Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease.

High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients.

Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice.

Cardiovascular disease is the most common comorbidity in patients with chronic kidney disease (CKD), affecting both their prognosis and quality of life. Cardiac fibrosis is common in patients with CKD with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-1ß, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) compared with Nx-salt mice treated with control rat rat IgG1 (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites, including histidine and γ-butyrobetaine, were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, antifibrotic, and partial antioxidative effects in the heart of Nx-salt mice.NEW & NOTEWORTHY In the present study, IL-6 blockade exerted anti-inflammatory, antifibrotic, and partial antioxidative effects on the hearts of mice with CKD on a high-salt diet. Therefore, IL-6 potentially mediates cardiac fibrosis induced by high salt intake in patients with CKD, a finding with therapeutic implications. Of note, the next therapeutic implication may simply be the reinforcement of low-salt diets or diuretics and further research on the anti-inflammatory effects of these measures rather than IL-6 blockade with high-salt diet.

Dependence of enhancement factor on electrode size for field emission current from carbon nanotube on silicon wafer.

This work studies the enhancement factor associated with a current emitted from a multi-wall carbon nanotube to an extremely small counter electrode. The experimental data show that the field enhancement factor increases by 1.15 times when the width of the counter electrode increases from 50 to 200 nm. To better understand this enhancement effect, field intensities at the emitter surface are numerically simulated. The experimental work and simulations demonstrate that the observed field enhancement results from increases in the capacitance between the emitter and counter electrode. In addition, corrugated counter electrodes are found to greatly affect both the capacitance and enhancement factor. This is because the corrugation of the anode surface raises the capacitance and thus provides a higher current. We experimentally show that an effective surface area enlargement of 1.67 times due to the corrugation provides a 1.06-fold increase of the enhancement factor. These results should assist in the future development of field emission devices based on semiconductor fabrication processes.

Surface effects on ionic Coulomb blockade in nanometer-size pores.

Ionic Coulomb blockade in nanopores is a phenomenon that shares some similarities but also differences with its electronic counterpart. Here, we investigate this phenomenon extensively using all-atom molecular dynamics of ionic transport through nanopores of about one nanometer in diameter and up to several nanometers in length. Our goal is to better understand the role of atomic roughness and structure of the pore walls in the ionic Coulomb blockade. Our numerical results reveal the following general trends. First, the nanopore selectivity changes with its diameter, and the nanopore position in the membrane influences the current strength. Second, the ionic transport through the nanopore takes place in a hopping-like fashion over a set of discretized states caused by local electric fields due to membrane atoms. In some cases, this creates a slow-varying 'crystal-like' structure of ions inside the nanopore. Third, while at a given voltage, the resistance of the nanopore depends on its length, the slope of this dependence appears to be independent of the molarity of ions. An effective kinetic model that captures the ionic Coulomb blockade behavior observed in MD simulations is formulated.

Electronic structure of α-sexithiophene ultrathin films grown on.

We investigated the electronic states of α-sexithiophene (α-6T) on by means of angle-resolved photoelectron spectroscopy using synchrotron radiation. The characteristic features of π states are observed in the valence region. The increase in the population of the S1 band, assigned to the surface state of , upon deposition of α-6T was measured and the change in the electron density was evaluated. The band diagram was constructed based on the measurement of the HOMO level and work function. The work function was found to change with the α-6T thickness in a characteristic manner. We constructed a model of the electron transfer at each growth stage based on the core levels of the substrate (Si 2p, Ag 3d) and α-6T molecule (C 1s, S 2p), as well as the valence state and work function change.

Flexibly designable wettability gradient for passive control of fluid motion via physical surface modification.

Modified solid surfaces exhibit unique wetting behavior, such as hydrophobicity and hydrophilicity. Such behavior can passively control the fluid flow. In this study, we experimentally demonstrated a wettability-designable cell array consisting of unetched and physically etched surfaces by reactive ion etching on a silicon substrate. The etching process induced a significant surface roughness on the silicon surface. Thus, the unetched and etched surfaces have different wettabilities. By adjusting the ratio between the unetched and etched surface areas, we designed one- and two-dimensional wettability gradients for the fluid channel. Consequently, fine-tuned channels passively realized unidirectional and curved fluid motions. The design of a wettability gradient is crucial for practical and portable systems with integrated fluid channels.

Artificial-intelligence-assisted mass fabrication of nanocantilevers from randomly positioned single carbon nanotubes.

Nanoscale cantilevers (nanocantilevers) made from carbon nanotubes (CNTs) provide tremendous benefits in sensing and electromagnetic applications. This nanoscale structure is generally fabricated using chemical vapor deposition and/or dielectrophoresis, which contain manual, time-consuming processes such as the placing of additional electrodes and careful observation of single-grown CNTs. Here, we demonstrate a simple and Artificial Intelligence (AI)-assisted method for the efficient fabrication of a massive CNT-based nanocantilever. We used randomly positioned single CNTs on the substrate. The trained deep neural network recognizes the CNTs, measures their positions, and determines the edge of the CNT on which an electrode should be clamped to form a nanocantilever. Our experiments demonstrate that the recognition and measurement processes are automatically completed in 2 s, whereas comparable manual processing requires 12 h. Notwithstanding the small measurement error by the trained network (within 200 nm for 90% of the recognized CNTs), more than 34 nanocantilevers were successfully fabricated in one process. Such high accuracy contributes to the development of a massive field emitter using the CNT-based nanocantilever, in which the output current is obtained with a low applied voltage. We further showed the benefit of fabricating massive CNT-nanocantilever-based field emitters for neuromorphic computing. The activation function, which is a key function in a neural network, was physically realized using an individual CNT-based field emitter. The introduced neural network with the CNT-based field emitters recognized handwritten images successfully. We believe that our method can accelerate the research and development of CNT-based nanocantilevers for realizing promising future applications.

Periodic switching of acoustic radiation force with beat created by multitone field.

Acoustic radiation force plays a key role in microfluidic systems for particle and cell manipulation. In this study, we investigate the acoustic radiation force resulting from synthesized ultrasounds that are emitted from multiple sound sources with slightly different oscillation frequencies. Due to the synthesized field, the acoustic radiation force is expressed as the sum of a dc component and harmonics of fundamental frequencies of a few hertz. This induces the beat of the acoustic radiation force. We demonstrate that the synthesized field provides the periodic on/off switching of the acoustic radiation force associated with the one denominational planar standing wave in a straight microfluidic channel. Consequently, our system can temporally manipulate acoustic radiation force without active controls.

Thermal oxidation process on Si(113)-(3 × 2) investigated using high-temperature scanning tunneling microscopy.

Thermal oxidation of Si(113) in a monolayer regime was investigated using high-temperature scanning tunneling microscopy (STM). Dynamic processes during thermal oxidation were examined in three oxidation modes - oxidation, etching, and transition modes - in the third of which both oxidation and etching occur. A precise temperature-pressure growth mode diagram was obtained via careful measurements for Si(113), and the results were compared with those for Si(111) in the present work and Si(001) in the literature. Initial oxidation processes were identified based on high-resolution STM images.

Mechanical Properties and Reliability of Parametrically Designed Architected Materials Using Urethane Elastomers.

Achieving multiple physical properties from a single material through three-dimensional (3D) printing is important for manufacturing applications. In addition, industrial-level durability and reliability is necessary for realizing individualized manufacturing of devices using 3D printers. We investigated the properties of architected materials composed of ultraviolet (UV)-cured urethane elastomers for use as insoles. The durability and reliability of microlattice and metafoam architected materials were compared with those composed of various foamed materials currently used in medical insoles. The hardness of the architected materials was able to be continuously adjusted by controlling the design parameters, and the combination of the two materials was effective in controlling rebound resilience. In particular, the features of the architected materials were helpful for customizing the insole properties, such as hardness, propulsive force, and shock absorption, according to the user's needs. Further, using elastomer as a component led to better results in fatigue testing and UV resistance compared with the plastic foam currently used for medical purposes. Specifically, polyethylene and ethylene vinyl acetate were deformed in the fatigue test, and polyurethane was mechanically deteriorated by UV rays. Therefore, these architected materials are expected to be reliable for long-term use in insoles.

Noise-induced switching from a symmetry-protected shallow metastable state.

We consider escape from a metastable state of a nonlinear oscillator driven close to triple its eigenfrequency. The oscillator can have three stable states of period-3 vibrations and a zero-amplitude state. Because of the symmetry of period-tripling, the zero-amplitude state remains stable as the driving increases. However, it becomes shallow in the sense that the rate of escape from this state exponentially increases, while the system still lacks detailed balance. We find the escape rate and show how it scales with the parameters of the oscillator and the driving. The results facilitate using nanomechanical, Josephson-junction based, and other mesoscopic vibrational systems for studying, in a well-controlled setting, the rates of rare events in systems lacking detailed balance. They also describe how fluctuations spontaneously break the time-translation symmetry of a driven oscillator.

Association between sinusitis and relapse and changes in the myeloperoxidase-antineutrophil cytoplasmic antibody in microscopic polyangiitis.

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7-54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19-4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14-5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Feasibility study applying a parametric model as the design generator for 3D-printed orthosis for fracture immobilization.

BACKGROUND: Applying 3D printing technology for the fabrication of custom-made orthoses provides significant advantages, including increased ventilation and lighter weights. Currently, the design of such orthoses is most often performed in the CAD environment, but creating the orthosis model is a time-consuming process that requires significant CAD experience. This skill gap limits clinicians from applying this technology in fracture treatment. The purpose of this study is to develop a parametric model as the design generator for 3D-printed orthoses for an inexperienced CAD user and to evaluate its feasibility and ease of use via a training and design exercise. RESULTS: A set of automatic steps for orthosis modeling was developed as a parametric model using the Visual Programming Language in the CAD environment, and its interface and workflow were simplified to reduce the training period. A quick training program was formulated, and 5 participants from a nursing school completed the training within 15 mins. They verified its feasibility in an orthosis design exercise and designed 5 orthoses without assistance within 8 to 20 mins. The few faults and program errors that were observed in video analysis of the exercise showed improvable weaknesses caused by the scanning quality and modeling process. CONCLUSIONS: Compared to manual modeling instruction, this study highlighted the feasibility of using a parametric model for the design of 3D-printed orthoses and its greater ease of use for medical personnel compared to the CAD technique. The parametric model reduced the complex process of orthosis design to a few minutes, and a customized interface and training program accelerated the learning period. The results from the design exercise accurately reflect real-world situations in which an inexperienced user utilizes a generator as well as demonstrate the utility of the parametric model approach and strategy for training and interfacing.

Rapid customization system for 3D-printed splint using programmable modeling technique - a practical approach.

BACKGROUND: Traditional splinting processes are skill dependent and irreversible, and patient satisfaction levels during rehabilitation are invariably lowered by the heavy structure and poor ventilation of splints. To overcome this drawback, use of the 3D-printing technology has been proposed in recent years, and there has been an increase in public awareness. However, application of 3D-printing technologies is limited by the low CAD proficiency of clinicians as well as unforeseen scan flaws within anatomic models.A programmable modeling tool has been employed to develop a semi-automatic design system for generating a printable splint model. The modeling process was divided into five stages, and detailed steps involved in construction of the proposed system as well as automatic thickness calculation, the lattice structure, and assembly method have been thoroughly described. The proposed approach allows clinicians to verify the state of the splint model at every stage, thereby facilitating adjustment of input content and/or other parameters to help solve possible modeling issues. A finite element analysis simulation was performed to evaluate the structural strength of generated models. A fit investigation was applied on fabricated splints and volunteers to assess the wearing experience. RESULTS: Manual modeling steps involved in complex splint designs have been programed into the proposed automatic system. Clinicians define the splinting region by drawing two curves, thereby obtaining the final model within minutes. The proposed system is capable of automatically patching up minor flaws within the limb model as well as calculating the thickness and lattice density of various splints. Large splints could be divided into three parts for simultaneous multiple printing. CONCLUSIONS: This study highlights the advantages, limitations, and possible strategies concerning application of programmable modeling tools in clinical processes, thereby aiding clinicians with lower CAD proficiencies to become adept with splint design process, thus improving the overall design efficiency of 3D-printed splints.

Driven nonlinear nanomechanical resonators as digital signal detectors.

Because of their nonlinearity, vibrational modes of resonantly driven nanomechanical systems have coexisting stable states of forced vibrations in a certain range of the amplitude of the driving force. Depending on its phase, which encodes binary information, a signal at the same frequency increases or decreases the force amplitude. The resulting force amplitude can be outside the range of bistability. The values of the mode amplitude differ significantly on the opposite sides of the bistability region. Therefore the mode amplitude is very sensitive to the signal phase. This suggests using a driven mode as a bi-directional bifurcation amplifier, which switches in the opposite directions depending on the signal phase and provides an essentially digital output. We study the operation of the amplifier near the critical point where the width of the bistability region goes to zero and thus the threshold of the signal amplitude is low. We also develop an analytical technique and study the error rate near the threshold. The results apply to a broad range of currently studied systems and extend to micromechanical systems and nonlinear electromagnetic cavities.