Search

Objectives: Until now, many researchers have conducted evaluations on hippocampi for analyses of cognitive dysfunction models using scopolamine. However, depending on the purposes of these analyses, there are differences in the experimental results for the hippocampi and cortexes. Therefore, this study intends to compare various analyses of cognitive dysfunction after scopolamine administration with each other in hippocampi and cortexes. Methods: Scopolamine was administered at three dosages in mice: 0.5, 1, and 3 mg/kg. And this study evaluates the differences in cognitive function and the expression of malondialdehyde (MDA), acetylcholinesterase (AChE), and brain-derived neurotrophic factor (BDNF) in mice's hippocampi and cortexes based on scopolamine dosages. Results: The Morris water maze test was conducted between 1 and 3 h after scopolamine injection to assess its duration. A significant decrease in behavioral ability was evaluated at 1 h, and we observed a similar recovery to the normal group at 3 h. And the Morris water maze escape latency showed differences depending on scopolamine concentration. While the escape waiting time in the control group and scop 0.5 administration group remained similar to that seen before administration, the administration of scop 1 and 3 increased it. In the experimental group administered scop 1 and 3, cerebral MDA levels in the cerebral cortex significantly increased. In the hippocampus, the MDA level in the scopolamine-administered groups slightly increased compared to the cortex. A Western blotting assay shows that Bax and Bcl-xl showed a tendency to increase or decrease depending on the concentration, but BDNF increased in scop 0.5, and scop 1 and 3 did not show a significant decrease compared to the control at the cerebral cortex. In the hippocampus, BDNF showed a concentration-dependent decrease in expression. Conclusions: This study's findings indicate that chemical analyses for MDA and AChE can be performed in the cerebral cortex, while the hippocampus is better suited for protein analysis of apoptosis and BDNF.

Despite the potential of oral immunotherapy against food allergy, adverse reactions and loss of desensitization hinder its clinical uptake. Dysbiosis of the gut microbiota is implicated in the increasing prevalence of food allergy, which will need to be regulated to enable for an effective oral immunotherapy against food allergy. Here we report an inulin gel formulated with an allergen that normalizes the dysregulated ileal microbiota and metabolites in allergic mice, establishes allergen-specific oral tolerance and achieves robust oral immunotherapy efficacy with sustained unresponsiveness in food allergy models. These positive outcomes are associated with enhanced allergen uptake by antigen-sampling dendritic cells in the small intestine, suppressed pathogenic type 2 immune responses, increased interferon-γ + and interleukin-10 + regulatory T cell populations, and restored ileal abundances of Eggerthellaceae and Enterorhabdus in allergic mice. Overall, our findings underscore the therapeutic potential of the engineered allergen gel as a suitable microbiome-modulating platform for food allergy and other allergic diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Herein, we report for the first time a simple strategy to design a hierarchical chemically exfoliated magnesium diboride and guar gum network structure decorated with Ru nanoparticles (eMgB 2 -GG@Ru) as an electrode to evaluate its electrochemical performance for the application of supercapacitor. The eMgB 2 and functionalized eMgB 2 -GG@Ru materials were thoroughly examined using XRD, TGA, DLS, FE-SEM, STEM, AFM, XPS, and BET techniques. The combined eMgB 2 -GG@Ru electrode exhibits a network structure morphology with an increased interlayer distance of eMgB 2 nanolayers along with a uniform distribution of spherical Ru nanoparticles. The electrochemical performance of eMgB 2 -GG@Ru and its pristine materials was studied through CV, GCD, and EIS to determine their supercapacitor performance. The eMgB 2 -GG@Ru electrode demonstrates higher specific capacitance (352 F/g) than its eMgB 2 @Ru (258.9 F/g), and MgB 2 (214.5 F/g) counterparts at a current density of 0.5 A/g in a three-electrode setup using 3 M KOH electrolyte. The hierarchical eMgB 2 -GG@Ru solid-state symmetric devices maintained higher capacity retention of 89 % even after 7000 cycles, achieving a maximum energy density of 26.12 kW/kg at the power density of 450 W/kg at 0.5 A/g. Therefore, the innovative eMgB 2 -GG@Ru electrode offers superior electrochemical performance with efficient electrolyte ion mobility for energy storage applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

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-Fe 2 O 3 decorated nanostructure with CC (CCIO) was achieved in situ pyrolysis of corn-husk and Fe(NO 3 ) 3 ·9H 2 O 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 Na 2 SO 4 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

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 MgB 2 flower-like nanostructures was developed via ecofriendly guar gum biopolymer substantial template (MgB 2 /GG@Ru NFS) and its photocatalytic performance was reported. Synthesis of MgB 2 @Ru, MgB 2 /GG@Ru NFS and commercial MgB 2 , was studied by FTIR, XRD, FE-SEM, EDX, AFM, TEM, UV-vis spectra, and XPS analysis. From the results, the MgB 2 /GG@Ru NFS exhibited a superior photocatalytic performance (99.7 %) than its precursors MgB 2 @Ru (79.7 %), and MgB 2 (53.7 %), with the degradation efficiency of the crystal violet (CV) within 100 min under visible light irradiation. The proposed photo-catalyst MgB 2 /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 MgB 2 /GG@Ru NFS was evaluated by trapping experiment of active species, verifying that superoxide (O 2 - ) and electron (e - ) contributed significant role in the dye degradation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

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., Competing Interests: The authors declare no competing interests., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

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., (© 2023. The Author(s).)

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., (© 2023. Korean Tissue Engineering and Regenerative Medicine Society.)

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., (© 2023. The Author(s).)

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., (© 2022. Korean Tissue Engineering and Regenerative Medicine Society.)

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., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interest exists., (Copyright © 2022. Published by Elsevier B.V.)

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 (T H 17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates T H 17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce T H 17-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 T H 17 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 T H 17 cells (and the levels of T H 17-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 T H 17-cell-mediated immune responses may have therapeutic potential., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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., (© The Author(s) 2022. Published by Oxford University Press.)

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., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Naik, Shimoga, Kim, Manjulatha, Subramanyam Reddy, Palem, Kumar, Kim and Lee.)

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.

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., (© 2021. The Author(s).)

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.

Polymer-clay nanocomposite hydrogel films (PCNCHFs) were prepared from caboxymethyl cellulose, polyvinylpyrrolidone, agar and nanosepiolite clay (0, 0.3, 0.5, 0.7, 0.9 and 1.5% reinforcement) by treating thermally in a simple, rapid, and inexpensive route. The PCNCHFs and its 5-fluorouracil (FU)-loaded composites (PCNCHFs@FU) were tested for FU release and characterized by FTIR, XRD, FE-SEM, EDX, DSC, and TGA analyses to investigate their structural, morphological, and thermal properties. The nanosepiolite-loaded polymer composites (PCNCHF1 to PCNCHF5) exhibited higher tensile strength than the pristine polymer hydrogel (PCNCHF0); consequently, the thermal properties (glass- and melting-transition) were improved. The PCNCHFs@FU demonstrated prolonged FU release at pH 7.4 for 32 h. The biocompatibility of PCNCHFs was tested against human skin fibroblast (CCDK) cells. The viability of cells exposed to all PCNCHFs was >95% after 72 h of culture. The live/dead assay show the proliferation of fibroblast cells, confirming the biocompatibility of the hydrogels. The pH-sensitive PCNCHFs@FU release could be suitable for drug release in cancer therapy, and the developed PCNCHFs may also be useful for tissue engineering, food packaging, and other biological applications., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

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.

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.

Extracellular matrix (ECM) remodeling is necessary for the development and self-healing of tissue, and the process is tissue specific. Matrix metalloproteinases (MMPs) play a role in ECM remodeling by unwinding and cleaving ECM. We hypothesized that ECM remodeling by MMPs is involved in the differentiation of stem cells into specific lineages during self-healing. To prove the hypothesis, we investigated which MMPs are involved in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) grown on a type I collagen (Col I) matrix, and we found that specifically high expression of MMP13 in hMSCs grown on a Col I matirx during osteogenic differentiation. Moreover, knocking down of MMP13 decreased the osteogenic differentiation of hMSCs grown on a Col I matrix. In addition, pre-treatment of recombinant human MMP13 lead to remodeling of Col I matrix and increased the osteogenic differentiation of hMSCs and in vivo bone formation following the upregulation of the expression of runt-related transcription factor 2 (RUNX2), integrin α3 (ITGA3), and focal adhesion kinase. Furthermore, the transcription factor RUNX2 bound to the MMP13 promoter. These results suggest that growth on a remodeled Col I matrix by MMP13 stimulates osteogenic differentiation of hMSCs and self-healing of bone tissue via an MMP13/ITGA3/RUNX2 positive feedback loop. STATEMENT OF SIGNIFICANCE: Self-healing of tissue could be the key to treating diseases that cannot be overcome by present technology. We investigated the mechanism underlying the self-healing of tissue and we found that the osteogenic differentiation was increased in hMSCs grown on a remodeled Col I matrix by the optimized concentration of MMP13 not in hMSCs grown on a Col I fragments cleaved by a high concentration of MMP13. In addition, we found the remodeled Col I matrix by MMP13 increased the osteogenic capacity through a MMP13/integrin α3/RUNX2 positive feedback loop. This result would be able to not only provide a strategy for bone tissue-specific functional materials following strong evidence about the self-healing mechanism of bone through the interaction between stem cells and the ECM matrix. As such, we strongly believe our finding will be of interest to researchers studying biomaterials, stem cell biology and matrix interaction for regenerative medicine and therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Here we report a self-supported SnO 2 nanofilm prepared by a robust electrochemical process as an electrocatalyst for the CO 2 reduction reaction. The SnO 2 film had a large surface area originating from its nano-architecture and manifested high selectivity toward formate (over 60%), which resulted in CO 2 -to-formate current density up to 33.66 mA cm -2 that is among the state-of-the-art. We unveiled that the high performance of the SnO 2 nanofilm is attributable to the presence of a metastable oxide under reductive conditions in addition to the abovementioned advantages.

The electrochemical CO 2 reduction reaction (CO 2 RR) using Cu-based catalysts holds great potential for producing valuable multi-carbon products from renewable energy. However, the chemical and structural state of Cu catalyst surfaces during the CO 2 RR remains a matter of debate. Here, we show the structural evolution of the near-surface region of polycrystalline Cu electrodes under in situ conditions through a combination of grazing incidence X-ray absorption spectroscopy (GIXAS) and X-ray diffraction (GIXRD). The in situ GIXAS reveals that the surface oxide layer is fully reduced to metallic Cu before the onset potential for CO 2 RR, and the catalyst maintains the metallic state across the potentials relevant to the CO 2 RR. We also find a preferential surface reconstruction of the polycrystalline Cu surface toward (100) facets in the presence of CO 2 . Quantitative analysis of the reconstruction profiles reveals that the degree of reconstruction increases with increasingly negative applied potentials, and it persists when the applied potential returns to more positive values. These findings show that the surface of Cu electrocatalysts is dynamic during the CO 2 RR, and emphasize the importance of in situ characterization to understand the surface structure and its role in electrocatalysis.

A high level of reactive oxygen species (ROS) such as hydrogen peroxide (H 2 O 2 ) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced H 2 O 2 will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through H 2 O 2 -responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for articular cartilage repair and regeneration. However, the terminal hypertrophic differentiation of Ad-MSC-derived cartilage is a critical barrier during hyaline cartilage regeneration. In this study, we investigated the role of matrilin-3 in preventing Ad-MSC-derived chondrocyte hypertrophy in vitro and in an osteoarthritis (OA) destabilization of the medial meniscus (DMM) model. Methacrylated hyaluron (MAHA) (1%) was used to encapsulate and make scaffolds containing Ad-MSCs and matrilin-3. Subsequently, the encapsulated cells in the scaffolds were differentiated in chondrogenic medium (TGF-β, 1-14 days) and thyroid hormone hypertrophic medium (T3, 15-28 days). The presence of matrilin-3 with Ad-MSCs in the MAHA scaffold significantly increased the chondrogenic marker and decreased the hypertrophy marker mRNA and protein expression. Furthermore, matrilin-3 significantly modified the expression of TGF-β2, BMP-2, and BMP-4. Next, we prepared the OA model and transplanted Ad-MSCs primed with matrilin-3, either as a single-cell suspension or in spheroid form. Safranin-O staining and the OA score suggested that the regenerated cartilage morphology in the matrilin-3-primed Ad-MSC spheroids was similar to the positive control. Furthermore, matrilin-3-primed Ad-MSC spheroids prevented subchondral bone sclerosis in the mouse model. Here, we show that matrilin-3 plays a major role in modulating Ad-MSCs' therapeutic effect on cartilage regeneration and hypertrophy suppression.

Background: Lipid polymer hybrid nanoparticles (LPHNPs) have been widely investigated in drug and gene delivery as well as in medical imaging. A knowledge of lipid-based surface engineering and its effects on how the physicochemical properties of LPHNPs affect the cell-nanoparticle interactions, and consequently how it influences the cytological response, is in high demand., Methods: Herein, we have engineered antibiotic-loaded (doxycycline or vancomycin) LPHNPs with cationic and zwitterionic lipids and examined the effects on their physicochemical characteristics (size and charge), antibiotic entrapment efficiency, and the in vitro intracellular bacterial killing efficiency against Mycobacterium smegmatis or Staphylococcus aureus infected macrophages., Results: The incorporation of cationic or zwitterionic lipids in the LPHNP formulation resulted in a size reduction in LPHNPs formulations and shifted the surface charge of bare NPs towards positive or neutral values. Also observed were influences on the drug incorporation efficiency and modulation of the drug release from the biodegradable polymeric core. The therapeutic efficacy of LPHNPs loaded with vancomycin was improved as its minimum inhibitory concentration (MIC) (2 µg/mL) versus free vancomycin (4 µg/mL). Importantly, our results show a direct relationship between the cationic surface nature of LPHNPs and its intracellular bacterial killing efficiency as the cationic doxycycline or vancomycin loaded LPHNPs reduced 4 or 3 log CFU respectively versus the untreated controls., Conclusion: In our study, modulation of surface charge in the nanomaterial formulation increased macrophage uptake and intracellular bacterial killing efficiency of LPHNPs loaded with antibiotics, suggesting alternate way for optimizing their use in biomedical applications., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Bose et al.)

Poly(acrylamide-co-acrylamidoglycolic acid)/guar gum@ Ag-nanocomposite (AgNC@PAAG) hydrogels has been fabricated by a green protocol utilizing rhubarb stem-extract as bioreductant. The prepared nanocomposites (NCs) are formulated by varying guar gum (GG) polymer and cross-linker content, and used remarkably to study the release of an anticancer drug, 5-fluorouracil (FU). The AgNC@PAAG has demonstrated its potential in bacterial inactivation and p-nitrophenol (PNP) reduction. The AgNC@PAAG hydrogels showed extended FU release time, which was up to 23 h in pH 7.4. The higher zone of inhibition was documented for AgNC@PAAG against B. subtilis and E. coli. It was noticed that, the inhibition activity of AgNC@PAAG, was directly proportional to cross-linker content than the GG polymer. The efficiency of AgNC@PAAG as a nanocatalyst was evaluated for a model reduction reaction of p-nitrophenol (PNP) reduction by aqueous sodium borohydride (NaBH 4 ), with an apparent rate constant of 121.8 × 10 -3  min -1 at ambient temperature. The proposed nanocatalysts are reliable and recyclable, demonstrated its catalytic recycle efficacy of 85% after the third successive run. These NCs robust its biological and catalytic activity after embedding silver nanoparticles (AgNPs) by the bioreduction process; these optimized nanocatalysts can be remarkably used in biomedical healthcare sectors and industrial catalysis., (Copyright © 2020. Published by Elsevier B.V.)

Background: Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome including unwanted adverse effects due to acidic pH, hypoxia, and limited nutrition. Matrilin-3 is an essential extracellular matrix (ECM) component during cartilage development and ossification and exerts chondrocyte protective effects., Methods: This study evaluated the effects of matrilin-3-primed adipose-derived MSCs (Ad-MSCs) on the repair of the degenerated disc in vitro and in vivo. We determined the optimal priming concentration and duration and developed an optimal protocol for Ad-MSC spheroid generation., Results: Priming with 10 ng/ml matrilin-3 for 5 days resulted in the highest mRNA expression of type 2 collagen and aggrecan in vitro. Furthermore, Ad-MSC spheroids with a density of 250 cells/microwell showed the increased secretion of favorable growth factors such as transforming growth factor beta (TGF-β1), TGF-β2, interleukin-10 (IL-10), granulocyte colony-stimulating factor (G-CSF), and matrix metalloproteinase 1 (MMP1) and decreased secretion of hypertrophic ECM components. In addition, matrilin-3-primed Ad-MSC spheroid implantation was associated with optimal repair in a rabbit model., Conclusion: Our results suggest that priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration.

Human pluripotent stem cells (hPSCs) are a potent source of clinically relevant mesenchymal stem cells (MSCs) that confer functional and structural benefits in cell therapy and tissue regeneration. Obtaining sufficient numbers of MSCs in a short period of time and enhancing the differentiation potential of MSCs can be offered the potential to improve the regenerative activity of MSCs therapy. In addition, the underlying processes in the isolation and derivation of MSCs from hPSCs are still poorly understood and controlled. To overcome these clinical needs, an efficient and simplified technique on the isolation of MSCs from spontaneously differentiated human embryonic stem cells (hESCs) via integrin α 5 β 1 (fibronectin (FN) receptor)-to-FN interactions (hESC-FN-MSCs) is successfully developed. It is demonstrated that hESC-FN-MSCs exhibit a typical MSC surface phenotype, cellular morphology, with the whole transcriptome similar to conventional adult MSCs; but show higher proliferative capacity, more efficient trilineage differentiation, enhanced cytokine secretion, and attenuated cellular senescence. In addition, the therapeutic potential and regenerative capacity of the isolated hESC-FN-MSCs are confirmed by in vitro and in vivo multilineage differentiation. This novel method will be useful in the generation of abundant amounts of clinically relevant MSCs for stem cell therapeutics and regenerative medicine., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis., Competing Interests: The authors declare no conflict of interest.

Statement of Problem: Patients with partial tooth loss treated with implant-supported fixed partial dentures (FPDs) have difficulty using conventional mandibular advancement devices (MADs) because of the risk of side effects. Also, which design factors affect biomechanical stability when designing MADs with better stability is unclear., Purpose: The purpose of this finite element (FE) analysis study was to analyze the effect of the MAD design on biomechanical behavior and to propose a new design process for improving the stability of MADs., Material and Methods: Each 3D model consisted of the maxillofacial bones, teeth, and implant-supported FPDs located in the left tooth loss area from the first premolar to the second molar and a MAD. Three types of custom-made MADs were considered: a complete-coverage MAD covering natural tooth-like conventional MADs, a shortened MAD excluding the coverage on the implant-supported FPD, and a newly designed MAD without anterior coverage. For the new MAD design, topology optimization was conducted to reduce the stress exerted on the teeth and to improve retention of the MAD. The new MAD design was finished by excluding the coverage of the maxillary and mandibular central incisors based on the results of the topology optimization. A mandibular posterior restorative force for a protrusion amount of 40% was used as the loading condition. The principal stress and pressure of the cancellous bone and periodontal ligaments (PDLs) were identified., Results: Considering the load concentration induced by the complete-coverage MAD, bone resorption risk and root resorption risk were observed at both ends of the mandibular teeth. The shortened MAD resulted in the highest stress concentration and pressure with the worst stability. However, in the case of the complete-coverage MAD, the pressure in the PDLs was reduced to the normal range, and the risk of root resorption was reduced., Conclusions: For patients with implant-supported FPDs, MAD designs with different extents of coverage had an influence on biomechanical behavior in terms of stress distribution in cancellous bone and PDLs. A MAD design without anterior coverage provided improved stability compared with complete-coverage or shortened designs. The presented method for MAD design, which combined FE analysis and topology optimization, could be effectively applied in the design of such improved MADs., (Copyright © 2019 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Health care and medicine were revolutionized in recent years by the development of biomaterials, such as stents, implants, personalized drug delivery systems, engineered grafts, cell sheets, and other transplantable materials. These materials not only support the growth of cells before transplantation but also serve as replacements for damaged tissues in vivo . Among the various biomaterials available, those made from natural biological sources such as extracellular proteins (collagen, fibronectin, laminin) have shown significant benefits, and thus are widely used. However, routine biomaterial-based research requires copious quantities of proteins and the use of pure and intact extracellular proteins could be highly cost ineffective. Gelatin is a molecular derivative of collagen obtained through the irreversible denaturation of collagen proteins. Gelatin shares a very close molecular structure and function with collagen and thus is often used in cell and tissue culture to replace collagen for biomaterial purposes. Recent technological advancements such as additive manufacturing, rapid prototyping, and three-dimensional printing, in general, have resulted in great strides toward the generation of functional gelatin-based materials for medical purposes. In this review, the structural and molecular similarities of gelatin to other extracellular matrix proteins are compared and analyzed. Current strategies for gelatin crosslinking and production are described and recent applications of gelatin-based biomaterials in cell culture and tissue regeneration are discussed. Finally, recent improvements in gelatin-based biomaterials for medical applications and future directions are elaborated. Impact statement In this study, we described gelatin's biochemical properties and compared its advantages and drawbacks over other extracellular matrix proteins and polymers used for biomaterial application. We also described how gelatin can be used with other polymers in creating gelatin composite materials that have enhanced mechanical properties, increased biocompatibility, and boosted bioactivity, maximizing its benefits for biomedical purposes. The article is relevant, as it discussed not only the chemistry of gelatin, but also listed the current techniques in gelatin/biomaterial manufacturing and described the most recent trends in gelatin-based biomaterials for biomedical applications.

In this literature, we discussed the effect of anti-reflection coating of silicon heterojunction (SHJ) solar cells with different characteristics of double layered indium tin oxide (ITO/ITO) structure. Firstly, the OPAL 2 simulation was performed to optimize the values of the photo generation-current density of ITO/ITO/Si device structures. Afterwards, experimental work was conducted by depositing ITO on the SHJ solar cell to analyze the anti-reflection coating effect. ITO was deposited on the SHJ solar cell for 90 to 180 seconds by varying the oxygen flow rate. The highest short-circuit current density of 39.25 mA/cm² was obtained when ITO was deposited for 150 seconds, which was higher than the short-circuit current density of non-deposited cell of ITO (38 mA/cm²). The efficiency of the SHJ solar cell increased by about 2% after additional ITO deposition to 20.75%, which was due to the improvement of short-circuit current density by ITO deposition. The double layer ITO helped to improve the efficiency of SHJ solar cell by increasing light absorption in a silicon wafer.

Owing to the importance of stem cell culture systems in clinical applications, researchers have extensively studied them to optimize the culture conditions and increase efficiency of cell culture. A spheroid culture system provides a similar physicochemical environment in vivo by facilitating cell-cell and cell-matrix interaction to overcome the limitations of traditional monolayer cell culture. In suspension culture, aggregates of adjacent cells form a spheroid shape having wide utility in tumor and cancer research, therapeutic transplantation, drug screening, and clinical study, as well as organic culture. There are various spheroid culture methods such as hanging drop, gel embedding, magnetic levitation, and spinner culture. Lately, efforts are being made to apply the spheroid culture system to the study of drug delivery platforms and co-cultures, and to regulate differentiation and pluripotency. To study spheroid cell culture, various kinds of biomaterials are used as building forms of hydrogel, film, particle, and bead, depending upon the requirement. However, spheroid cell culture system has limitations such as hypoxia and necrosis in the spheroid core. In addition, studies should focus on methods to dissociate cells from spheroid into single cells.

The directed differentiation of human adipose-derived stem cells (hASCs) into different cell types has shown great therapeutic potential in treating various diseases. To maximize the therapeutic potentials, researchers have tried manipulating master transcriptional genes that promote efficient differentiation of mesenchymal stem cells (MSCs) such as the MAPK/ERK signaling pathway. Sprouty (SPRY) is a family of proteins that are known to inhibit the MAPK/ERK signaling pathway. Although the role of some SPRY isoforms in MSC differentiation is known, the function of SPRY4 isoform has not been fully elucidated. In the present study, the role of SPRY4 in the multilineage differentiation of hASCs has been elucidated. To investigate the role of SPRY4 in hASC differentiation and tissue regeneration, we performed a transient knockdown of SPRY expression via a small interfering RNA (siSPRY4). Western blot and quantitative polymerase chain reaction results revealed that the treatment of siSPRY4 before induction of differentiation had no significant effect on adipogenic, but reduced chondrogenic, differentiation of hASCs. Interestingly, SPRY4 transient knockdown had a significant effect on the osteogenic differentiation as indicated by the increased messenger RNA (mRNA) and protein expression of osteogenic markers such as alkaline phosphatase (ALP; 2.3-fold) and osteopontin (OPN; 3.5-fold) and increased calcium deposition measured via Alizarin red staining (3.3-fold). Moreover, in vivo tissue regeneration of siSPRY4-treated hASCs in ectopic bone formation and calvarial defect mouse models showed higher bone volume (5.24-fold) and trabecular number (4.59-fold) assessed via histological and microcomputed tomography analyses. We also determined that the enhanced osteogenic differentiation in SPRY4-treated hASCs was due to the induction of ERK1/2 phosphorylation. Taken together, our results suggest that the regulation of SPRY4 through MAPK signaling is a potentially critical aspect on the osteogenic differentiation of hASCs and for bone tissue regeneration, and thus, may be utilized as a potent technique in the development of effective bone therapeutics. Impact Statement This study tried to expand our current understanding of the osteogenic differentiation of mesenchymal stem cells. The transient downregulation of the SPRY4 expression via small interfering RNA (siRNA) showed significant enhancement of the osteogenic differentiation of adipose-derived stem cells via the induction of ERK 1/2 phosphorylation. This suggests the possible mechanism to maximize the potential of stem cell as therapeutics and has a great potential in treating various bone-related diseases.

Most traditional vaccines are composed either of a whole pathogen or its parts; these vaccines, however, are not always effective and can even be harmful. As such, additional agents known as adjuvants are necessary to increase vaccine safety and efficacy. This review summarizes the potential of biodegradable materials, including synthetic and natural polymers, for vaccine delivery. These materials are highly biocompatible and have minimal toxicity, and most biomaterial-based vaccines delivering antigens or adjuvants have been shown to improve immune response, compared to formulations consisting of the antigen alone. Therefore, these materials can be applied in modern vaccine development., (© 2019 Published by Elsevier B.V. on behalf of The Korean Society of Industrial and Engineering Chemistry.)

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans -cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b + myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.

Cholesterol and lipid metabolism are associated with osteoarthritis (OA) in human cartilage. High cholesterol levels in OA chondrocytes leads to decreased membrane fluidity and blocks the signaling cascade associated with the expression of chondrogenic genes. It is known that bile acid plays a role in regulating cholesterol homeostasis and the digestion of fats in the human body. Tauroursodeoxycholic acid (TUDCA), as a member of the bile acid family, also aids in the transport of cellular cholesterol. In this study, we hypothesized that TUDCA might be able to promote the restoration of OA cartilage by reducing membrane cholesterol levels in OA chondrocytes and by stimulating the chondrogenic signaling cascade. To assess this hypothesis, we investigated the effects of TUDCA on degenerated chondrocytes isolated from patients with OA. Importantly, treatment with TUDCA at sub-micellar concentrations (2500 μM) significantly increased cell proliferation and Cyclin D1 expression compared with the controls. In addition, the expression of chondrogenic marker genes (SOX9, COL2, and ACAN), proteins (SOX9 and COL2), and glycosaminoglycan (Chondroitin sulfate) was much higher in the TUDCA-treated group compared to the controls. We also found that TUDCA treatment significantly reduced the intracellular cholesterol levels in the chondrocytes and increased membrane fluidity. Furthermore, the stability of TGF receptor 1 and activity of focal adhesion proteins were also increased following TUDCA treatment. Together, these results demonstrated that TUDCA could be used as an alternative treatment for the restoration of OA cartilage.

Biocompatible, electrically conductive microfibers with superior mechanical properties have received a great attention due to their potential applications in various biomedical applications such as implantable medical devices, biosensors, artificial muscles, and microactuators. Here, we developed an electrically conductive and mechanically stable carbon nanotube-based microactuator with a low degradability that makes it usable for an implantable device in the body or biological environments. The microfiber was composed of hyaluronic acid (HA) hydrogel and single-wall carbon nanotubes (SWCNTs) (HA/SWCNT). HA hydrogel acts as biosurfactant and ion-conducting binder to improve the dispersion of SWCNTs resulting in enhanced electrical and mechanical properties of the hybrid microfiber. In addition, HA was crosslinked to prevent the leaking of the nanotubes from the composite. Crosslinking of HA hydrogel significantly enhances Young's modulus, the failure strain, the toughness, the stability of the electrical conductivity, and the resistance to biodegradation and creep of hybrid microfibers. The obtained crosslinked HA/SWCNT hybrid microfibers show an excellent capacitance and actuation behavior under mechanical loading with a low potential of ±1 V in a biological environment. Furthermore, the HA/SWCNT microfibers exhibit an excellent in vitro viability. Finally, the biocompatibility is shown through the resolution of an early inflammatory response in less than 3 weeks after the implantation of the microfibers in the subcutaneous tissue of mice.

The effect of porous structures on the electrocatalytic activity of N-doped carbon is studied by using electrochemical analysis techniques and the result is applied to synthesize highly active and stable Fe-N-C catalyst for oxygen reduction reaction (ORR). We developed synthetic procedures to prepare three types of N-doped carbon model catalysts that are designed for systematic comparison of the porous structures. The difference in their catalytic activity is investigated in relation to the surface area and the electrochemical parameters. We found that macro- and mesoporous structures contribute to different stages of the reaction kinetics. The catalytic activity is further enhanced by loading the optimized amount of Fe to prepare Fe-N-C catalyst. In both N-doped carbon and Fe-N-C catalysts, the hierarchical porous structure improved electrocatalytic performance in acidic and alkaline media. The optimized catalyst exhibits one of the best ORR performance in alkaline medium with excellent long-term stability in anion exchange membrane fuel cell and accelerated durability test. Our study establishes a basis for rationale design of the porous carbon structure for electrocatalytic applications.

Background: Ell3 is a RNA polymerase II elongation factor that has various cell type-dependent functions, such as regulating the differentiation efficiency of embryonic stem cells and sensitizing cancer cells to anticancer drugs. However, there has been little research on the role of Ell3 on the regulation of senescence and apoptosis of stem cells., Methods: We analyzed the senescence of Ell3-suppressed stem cells by mitochondrial activity, β-gal (+) cells, and lineage differentiation efficiency. The apoptosis of Ell3-overexpressing stem cells was analyzed by Annexin V staining, Immunoblot, and Live&dead assay. In addition, chromatin immunoprecipitation and luciferase assays were used to demonstrate p53 functions as a direct transcriptional activator of Ell3., Results: Suppression of Ell3 expression induced senescence in stem cells by increasing Bcl-2 expression. Unlike the effect of Ell3 suppression, the ectopic expression of Ell3 induces apoptosis of stem cells and induces apoptosis of adjacent cells. In addition, p53 functions as a direct transcriptional activator of Ell3 during the stem cell apoptosis., Conclusions: We suggest that the function of Ell3 is associated with the p53-Bcl2 axis in both senescent and apoptotic ADSCs.

The aim of this study was to investigate the anti-inflammatory effects by ursodeoxycholic acid (UDCA) in rats with a spinal cord injury (SCI). A moderate mechanical compression injury was imposed on adult Sprague-Dawley (SD) rats. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale and the tissue volume of the injured region was analyzed using hematoxylin and eosin staining. The pro-inflammatory factors were evaluated by immunofluorescence (IF) staining, a quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). The phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways related to inflammatory responses were measured by Western blot assays. UDCA improved the BBB scores and promoted the recovery of the spinal cord lesions. UDCA inhibited the expression of glial fibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α), ionized calcium-binding adapter molecule 1 (iba1), and inducible nitric oxide synthase (iNOS). UDCA decreased the pro-inflammatory cytokines of TNF-α, interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in the mRNA and protein levels. UDCA increased the anti-inflammatory cytokine interleukin 10 (IL-10) in the mRNA and protein levels. UDCA suppressed the phosphorylation of ERK, JNK, and the p38 signals. UDCA reduces pro-inflammatory responses and promotes functional recovery in SCI in rats. These results suggest that UDCA is a potential therapeutic drug for SCI.

Bioengineering strategies to enhance the natural targeting function of nanocarriers would expand their therapeutic applications. Here, we designed bioengineered stem cell membrane-functionalized nanocarriers (BSMNCs) harboring C-X-C chemokine receptor type 4 (CXCR4) to achieve robust targeting and also to increase their retention time in ischemic tissue. Stem cell membrane coated nanocarrier (SMNCs) or poly (lactic-co-glycolic acid) (PLGA) nanocarriers (PNCs) and BSMNCs were prepared by functionalizing PNCs with human adipose-derived stem cells (hASCs) membranes and hASCs engineered to overexpress CXCR4-receptor, respectively. The functionalization of PNCs with stem cell membranes derived from hASCs significantly enhance the nanocarrier penetration across endothelial cell barrier compare to PNCs. In addition, stem cell membrane functionalization on PNCs also significantly decreased the nanoparticles uptake in J774 (murine) and THP (human) macrophages respectively from 84% to 76%-29% and 24%. Interestingly, BSMNCs showed much higher level of accumulation in ischemic tissue than SMNCs. Systemic retro-orbital injection of BSMNCs loaded with VEGF into mice with hindlimb ischemia resulted substantially enhancement of blood reperfusion, muscle repair, and limb salvage compared to animals treated with SMNCs loaded with similar concentration of VEGF. The reported strategy could be used to create biocompatible and custom-tailored biomimetic nanoparticles with various hybrid functionalities, which may overcome the limitations of current nanoparticle-based therapeutic and imaging platforms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Transient receptor potential vanilloid type 4 (TRPV4) was originally described as a calcium-permeable nonselective cation channel. TRPV4 is now recognized as a polymodal ionotropic receptor: it is a broadly expressed, nonselective cation channel (permeable to calcium, potassium, magnesium, and sodium) that plays an important role in a multitude of physiological processes. TRPV4 is involved in maintaining homeostasis, serves as an osmosensor and thermosensor, can be activated directly by endogenous or exogenous chemical stimuli, and can be activated or sensitized indirectly via intracellular signaling pathways. Additionally, TRPV4 is upregulated in a variety of pathological conditions. In this review, we focus on the role of TRPV4 in mediating homeostasis and pathological events in the central nervous system (CNS). This review is composed of three parts. Section 1 describes the role of TRPV4 in maintaining homeostatic processes, including the volume of body water, ionic concentrations, volume, and the temperature. Section 2 describes the effects of activation and inhibition of TRPV4 in the CNS. Section 3 focuses on the role of TRPV4 during pathological events in CNS.

[This corrects the article DOI: 10.3389/fphar.2018.00445.].