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Nitric oxide (NO), a radical gas molecule produced by nitric oxide synthase, plays a key role in the human body. However, when endogenous NO is overproduced by physiological disorders, severe inflammatory diseases such as rheumatoid arthritis (RA) can occur. Therefore, scavenging NO may be an alternative strategy for treating inflammatory disorders. In our previous study, we developed a NO-responsive macrosized hydrogel by incorporating a NO-cleavable cross-linker (NOCCL); here, we further evaluate the effectiveness of the NO-scavenging nanosized hydrogel (NO-Scv gel) for treating RA. NO-Scv gel is simply prepared by solution polymerization between acrylamide and NOCCL. When the NO-Scv gel is exposed to NO, NOCCL is readily cleaved by consuming the NO molecule, as demonstrated in a Griess assay. As expected, the NO-Scv gel reduces inflammation levels by scavenging NO in vitro and shows excellent biocompatibility. Furthermore, the more promising therapeutic effect of the NO-Scv gel in suppressing the onset of RA is observed in vivo in a mouse RA model when compared to the effects of dexamethasone, a commercial drug. Therefore, our findings suggest the potential of the NO-Scv gel for biomedical applications and further clinical translation.

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Periacetabular osteotomy (PAO) is a complex surgical procedure to restore acetabular coverage in the dysplastic hip, and the amount of acetabular rotation during PAO plays a key role. Using computational simulations, this study assessed the optimal direction and amount of the acetabular rotation in three dimensions for a patient undergoing PAO. Anatomy-specific finite element (FE) models of the hip were constructed based on clinical CT images. The calculated acetabular rotation during PAO were 9.7°, 18°, and 4.3° in sagittal, coronal, and transverse planes, respectively. Based on the actual acetabular rotations, twelve postoperative FE models were generated. An optimal position was found by gradually varying the amount of the acetabular rotations in each anatomical plane. The coronal plane was found to be the principal rotational plane, which showed the strongest effects on joint contact pressure compared to other planes. It is suggested that rotation in the coronal plane of the osteotomized acetabulum is one of the primary surgical parameters to achieve the optimal clinical outcome for a given patient.

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Nitric oxide (NO) is a crucial signaling molecule with various functions in physiological systems. Due to its potent biological effect, the preparation of responsive biomaterials upon NO having temporally transient properties is a challenging task. This study represents the first therapeutic-gas (i.e., NO)-responsive hydrogel by incorporating a NO-cleavable crosslinker. The hydrogel is rapidly swollen in response to NO, and not to other gases. Furthermore, the NO-responsive gel is converted to enzyme-responsive gels by cascade reactions from an enzyme to NO production for which the NO precursor is a substrate of the enzyme. The application of the hydrogel as a NO-responsive drug-delivery system is proved here by revealing effective protein drug release by NO infusion, and the hydrogel is also shown to be swollen by the NO secreted from the cultured cells. The NO-responsive hydrogel may prove useful in many applications, for example drug-delivery vehicles, inflammation modulators, and as a tissue scaffold.

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In this study, we designed NO-activatable gold nanoparticles (NAM-AuNPs) for specific targeting and photo-thermal ablation of macrophages. The gold nanoparticles showed aggregation behavior in response to NO solution as well as endogenous NO secreted from activated macrophages. Following NIR irradiation, significant cytotoxicity was observed in activated RAW 264.7 cells treated with NAM-AuNPs.

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A biocompatible nitric oxide (NO) delivery nanoplatform, whose structure is a hollow nanoparticle composed of polydopamine backbone and diazeniumdiolates functional groups, is developed for antibacterial therapy. This platform liberates high NO quantitis and exerts the antibacterial activity with excellent biocompatibility thus being promising for treating bacterial infections.

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Amyloid fibrils are insoluble protein aggregates comprised of highly ordered ß-sheet structures and they are involved in the pathology of amyloidoses, such as Alzheimer's disease. A supramolecular strategy is presented for inhibiting amyloid fibrillation by using cucurbit[7]uril (CB[7]). CB[7] prevents the fibrillation of insulin and ß-amyloid by capturing phenylalanine (Phe) residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. These results suggest that the Phe-specific binding of CB[7] can modulate the intermolecular interaction of amyloid proteins and prevent the transition from monomeric to multimeric states. CB[7] thus has potential for the development of a therapeutic strategy for amyloidosis.

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DNA-templated silver nanoclusters (DNA-AgNCs) have emerged as promising materials for sensing, bio-labelling, and bio-imaging due to their fluorogenic properties. Using the 12 mer DNA with a cytosine-rich sequence, AgCNs have been formed successfully. Herein, we develop two different types of DNA-AgNC systems for the detection of potassium ions (K+) and nitric oxide (NO) by utilizing the structural change of DNA or DNA template transformation. In K+ detection, a thrombin binding aptamer (TBA) was utilized as both the AgNC template and the K+ binding probe. The fluorescence emission of the DNA1-AgNC probe was diminished proportionally to the amount of K+ detected, which transforms the AgNC-adapted structure into G-quadruplex. On the other hand, NO detection has been accomplished by NO-induced deamination of cytosine. The structural change of cytosine to deoxyuridine destabilizes the DNA2-AgNC structure, resulting in quenching of fluorescence intensity. The characteristics of these two highly quantitative detection probes were analysed by UV absorption, fluorescence emission, and transmission electron microscopy (TEM). Each system provides a detection limit of 6.2 µM for K+ and 0.1 µM for NO. We expect that these systems enable the opening of a new horizon for highly sensitive and selective detection systems.

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The work demonstrated a successful synthesis of nitric oxide (NO)-releasing material and its antibacterial effect on Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA). The polymeric support composed of thermosensitive Pluronic F68 having good biocompatibility and branched polyethylenimine (BPEI) housed N-diazeniumdiolates (NONOates) which could store and release NO under appropriate physiological condition. The developed F68-BPEI-NONOates releases a sufficient amount of NO under physiological condition to elicit effective killing of E. coli, S. aureus and MRSA. The antibacterial ability of the released NO was compared to untreated control or unmodified F68 polymer by using confocal microscopy; F68-BPEI-NONOates demonstrated excellent antibacterial activity with in vitro low cytotoxicity. TEM investigation also revealed the destruction of bacteria membrane caused by NO. The effectiveness of F68-BPEI-NONOates against resistant strains such as MRSA provides a very simple but highly efficient strategy to combat drug-resistant bacterial infections.

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The first objective of this study was to determine the kinematic variability of the lower extremity joints using methods from the mathematical chaos theory in a normal walking environment in conjunction with a large population of healthy young adults. The second objective was to test the hypothesis that variability characteristics are different between joints and to further investigate differences between male and female and right and left subgroups. A total of forty young healthy subjects (20 males: 24.1+/-3.1 years; 20 females: 22.5+/-3.2 years) volunteered, and their joint motions were captured while walking on a treadmill for 90 s in order to estimate Lyapunov Exponent (LE) values. Means and standard deviations of the LEs ranged from 0.035+/-0.016 (right ankle) to 0.073+/-0.023 (left knee) for the male subjects and from 0.028+/-0.014 (left ankle) to 0.065+/-0.028 (right hip) for the female subjects. Between the males and females, differences in LEs were observed to be statistically significant only for the left knee. There were no statistically significant differences between the right and left sides of the joints. However, differences between joints were statistically significant except between the hip and knee. These results are the first such comparison of the variability in the lower extremity without the confounding effect of walking speed on the variability of joint motions, and can serve as a normative database.

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