Large-Area Silicon Nitride Nanosieve for Enhanced Diffusion-Based Exosome Isolation.

Nanoporous membranes have a variety of applications, one of which is the size-selective separation of nanoparticles. In drug delivery, nanoporous membranes are becoming increasingly important for the isolation of exosomes, which are bio-nanoparticles. However, the low pore density and thickness of commercial membranes limit their efficiency. There have been many attempts to fabricate sub-micrometer thin membranes, but the limited surface area has restricted their practicality. In this study, large-area silicon nitride nanosieves for enhanced diffusion-based isolation of exosomes are presented. Notably, these nanosieves are scaled to sizes of up to 4-inch-wafers, a significant achievement in overcoming the fabrication challenges associated with such expansive areas. The method employs a 200 nm porous sieve (38.2% porosity) for exosome separation and a 50 nm sieve (10.7% porosity) for soluble protein removal. These 300 nm thick nanosieves outperform conventional polycarbonate membranes by being 50 times thinner, thereby increasing nanoparticle permeability. The method enables a 90% recovery rate of intact exosomes from human serum and a purity ratio of 3 × 107 particles/µg protein, 4.6 times higher than ultracentrifugation methods. The throughput of the method is up to 15 mL by increasing the size of the nanosieve, making it an ideal solution for large-scale exosome production for therapeutic purposes.

Fast Reconfigurable Electrode Array Based on Titanium Oxide for Localized Stimulation of Cultured Neural Network.

Planar microelectrode arrays have become standard tools for in vitro neural-network analysis. However, these predefined micropatterned devices lack adaptability to target-specific cells within a cultured network. Herein, we fabricated a reconfigurable TiO2 electrode array with an anatase-brookite bicrystalline polymorphous mesoporous layer. Because of its selective absorption of ultraviolet (UV) light and corresponding photoconductivity, TiO2 electrode array was identified as a promising tool for high-resolution light-addressing. The TiO2 film was used as a semitransparent semiconductor with a high Roff/Ron ratio of 105 and a fast response time of 400 ms. In addition, the effect of UV radiation on the resistance of the TiO2 film over 30 d in an aqueous environment was analyzed, with the film exhibiting high stability. An arbitrary UV pattern was applied to a reconfigurable TiO2 electrode using a digital micromirror device (DMD), affording highly localized neural stimulation at the single-cell level. The reconfigurable TiO2 electrode with a patterned indium tin oxide (ITO) substrate enabled the independent connection of up to 60 points with external stimulators and signal recorders. We believe this technique would be helpful for electrophysiological research requiring the analysis of cell and neural-network features using a highly localized neural interface.

Permanent Anticoagulation Blood-Vessel by Mezzo-Sized Double Re-Entrant Structure.

Having a permanent omniphobicity on the inner surface of the tube can bring enormous advantages, such as reducing resistance and avoiding precipitation during mass transfer. For example, such a tube can prevent blood clotting when delivering blood composed of complex hydrophilic and lipophilic compounds. However, it is very challenging to fabricate micro and nanostructures inside a tube. To overcome these, a wearability and deformation-free structural omniphobic surface is fabricated. The omniphobic surface can repel liquids by its "air-spring" under the structure, regardless of surface tension. Furthermore, it is not lost an omniphobicity under physical deformation like curved or twisted. By using these properties, omniphobic structures on the inner wall of the tube by the "roll-up" method are fabricated. Fabricated omniphobic tubes still repels liquids, even complex liquids like blood. According to the ex vivo blood tests for medical usage, the tube can reduce thrombus formation by 99%, like the heparin-coated tube. So, the surface will soon replace typical coating-based medical surfaces or anticoagulation blood vessels.

Anti-Obesity and Anti-Adipogenic Effects of Administration of Arginyl-Fructose-Enriched Jeju Barley (Hordeum vulgare L.) Extract in C57BL/6 Mice and in 3T3-L1 Preadipocytes Models.

In our previous study, we reported that arginyl-fructose (AF), one of the Amadori rearrangement compounds (ARCs) produced by the heat processing of Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. This reduced absorption of carbohydrate might be helpful to control body weight gain due to excessive carbohydrate consumption and support induced calorie restriction. However, the weight management effect, except for the effect due to anti-hyperglycemic action, along with the potential mechanism of action have not yet been determined. Therefore, the efforts of this study are to investigate and understand the possible weight management effect and mechanism action of AF-enriched barley extracts (BEE). More specifically, the effect of BEE on lipid accumulation and adipogenic gene expression, body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated using C57BL/6 mice and 3T3-L1 preadipocytes models. The formation of lipid droplets in the 3T3-L1 treated with BEE (500 and 750 µg/mL) was significantly blocked (p < 0.05 and p < 0.01, respectively). Male C57BL/6 mice were fed a high-fat diet (30% fat) for 8 weeks with BEE (0.3 g/kg-body weight). Compared to the high fat diet control (HFD) group, the cells treated with BEE significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (CEBP/α), the mRNA expression of downstream lipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c (SREBP-1c). Supplementation of BEE effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to the HFD group, BEE significantly suppressed body weight gain (16.06 ± 2.44 g vs. 9.40 ± 1.39 g, p < 0.01) and increased serum adiponectin levels, significantly, 1.6-folder higher than the control group. These results indicate that AF-enriched barley extracts may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Diffusion-Based Separation of Extracellular Vesicles by Nanoporous Membrane Chip.

Extracellular vesicles (EVs) have emerged as novel biomarkers and therapeutic material. However, the small size (~200 nm) of EVs makes efficient separation challenging. Here, a physical/chemical stress-free separation of EVs based on diffusion through a nanoporous membrane chip is presented. A polycarbonate membrane with 200 nm pores, positioned between two chambers, functions as the size-selective filter. Using the chip, EVs from cell culture media and human serum were separated. The separated EVs were analyzed by nanoparticle tracking analysis (NTA), scanning electron microscopy, and immunoblotting. The experimental results proved the selective separation of EVs in cell culture media and human serum. Moreover, the diffusion-based separation showed a high yield of EVs in human serum compared to ultracentrifuge-based separation. The EV recovery rate analyzed from NTA data was 42% for cell culture media samples. We expect the developed method to be a potential tool for EV separation for diagnosis and therapy because it does not require complicated processes such as immune, chemical reaction, and external force and is scalable by increasing the nanoporous membrane size.

Harmful algal blooms and liver diseases: focusing on the areas near the four major rivers in South Korea.

Freshwater harmful algal blooms (HABs) have become a global concern because blooms contain cyanotoxins that can cause liver damage and other negative health impacts. In South Korea, HABs have been frequently observed along the major rivers (Han, Geum, Nakdong, and Youngsan) in recent years. However, there are hardly any studies that report a linkage between HABs and human health, especially along the four major rivers where dams, weirs, and reservoirs were constructed, and sediments were dredged under the Four Major Rivers Project (FMRP) that ended in 2012. The goals of this study were to summarize spatial distribution patterns of HABs and investigate a potential association between HABs and liver diseases. Chlorophyll-a concentration was used to estimate bloom intensity since it was the only available bloom-related parameter that covers the entire rivers. Liver disease data (ICD-10 codes: K71-K77) were sorted by administrative districts. Generalized linear mixed model was used to analyze the bloom, liver diseases, and population data (2005-2016). The results show that chlorophyll-a levels significantly increased since 2013, except Han River region. There was a significant association between HAB intensity and incidence rate of liver diseases, except Han River area, and the extent of association significantly increased after the completion of the FMRP. For future studies, more in-depth epidemiological investigations are warranted in those areas to accurately determine more specific associations between HABs and liver diseases as well as other bloom-related diseases and symptoms. In addition, identification of major exposure pathways to cyanotoxins is needed to better protect public health in those bloom-affected areas.

Flexible and Stable Omniphobic Surfaces Based on Biomimetic Repulsive Air-Spring Structures.

In artificial biological circulation systems such as extracorporeal membrane oxygenation, surface wettability is a critical factor in blood clotting problems. Therefore, to prevent blood from clotting, omniphobic surfaces are required to repel both hydrophilic and oleophilic liquids and reduce surface friction. However, most omniphobic surfaces have been fabricated by combining chemical reagent coating and physical structures and/or using rigid materials such as silicon and metal. It is almost impossible for chemicals to be used in the omniphobic surface for biomedical devices due to durability and toxicity. Moreover, a flexible and stable omniphobic surface is difficult to be fabricated by using conventional rigid materials. This study demonstrates a flexible and stable omniphobic surface by mimicking the re-entrant structure of springtail's skin. Our surface consists of a thin nanohole membrane on supporting microstructures. This structure traps air under the membrane, which can repel the liquid on the surface like a spring and increase the contact angle regardless of liquid type. By theoretical wetting model and simulation, we confirm that the omniphobic property is derived from air trapped in the structure. Also, our surface well maintains the omniphobicity under a highly pressurized condition. As a proof of our concept and one of the real-life applications, blood experiments are performed with our flat and curved surfaces and the results including contact angle, advancing/receding angles, and residuals show significant omniphobicity. We hope that our omniphobic surface has a significant impact on blood-contacting biomedical applications.

Anatomic study to determine a safe surgical reference point for mandibular ramus osteotomy.

OBJECTIVE: The purpose of this study was to identify a surgical reference point on the mandibular ramus that can be used during ramus osteotomy to prevent injury to the inferior alveolar nerve. MATERIALS AND METHODS: A total of 125 subjects' mandibles were analyzed and compared on a three-dimensional (3D) model constructed from computed tomography (CT). 25 volunteer subjects with normal class I occlusion (group I, control), 50 consecutive subjects (25 females and 25 males) diagnosed with mandibular retrognathism (group II), and 50 consecutive subjects (25 females and 25 males) with prognathism (group III) were included. This study created a landmark (the midwaist point) at the halfway point on a horizontal plane between the most concave points on the anterior and posterior borders of mandibular ramus, with the vertical plane bisecting the horizontal plane. The midwaist point was compared to other anatomic landmarks including antilingula, lingula, and mandibular foramen for correlation. RESULTS: The distance from the midwaist point to lingula and mandibular foramen along the horizontal plane was not significantly different among three groups. Lingula and mandibular foramen were mostly located within 2 mm posterior of the midwaist point, whereas the locations of lingula and mandibular foramen along the vertical plane to the midwaist point were highly variable. CONCLUSION: The midwaist point is an excellent intraoperative reference point that can help surgeons to identify the position of the lingual and the mandibular foramen, thus preventing inferior alveolar nerve injury.

Partial Necrosis of the Mandibular Proximal Segment Following Transoral Vertical Ramus Osteotomy.

Transoral vertical ramus osteotomy (TOVRO) procedure can result in a variety of complications. Complications commonly reported include extensive bleeding due to major blood vessel injury, unpredictable fracture, postoperative infection, neurosensory deficit related Inferior alveolar nerve, insufficient osteosynthesis, and temporomandibular joint problem. The authors describe a case of partial necrosis of the mandibular proximal segment following TOVRO, a rarely reported complication. A 37-year-old otherwise healthy woman underwent Lefort l osteotomy and TOVRO to correct mandibular prognathism. Postoperatively, she developed pain and swelling in the right submandibular region and was found to have a partial necrosis of proximal segment.

Long-term results of vertical height augmentation genioplasty using autogenous iliac bone graft.

OBJECTIVE: In order to clarify the clinical utility of the vertical height augmentation (VHA) genioplasty using autogenous iliac bone graft (IBG), this study examined the postsurgical changes in hard and soft tissues of the chin and the stability of the grafted bone. STUDY DESIGN: Twenty-three patients who had undergone VHA genioplasty using autogenous IBG were evaluated radiographically and clinically. A comparison study of the changes in hard to soft tissues after surgery in all 23 patients was performed with preoperative, 1-month, 3-months, 6-months, and/or 1-year postoperative lateral cephalograms by tracing. Stability, bone healing, and complication of the grafted bone was evaluated by follow-up radiographs and clinical observation. RESULTS: Between the preoperative and 6-month postoperative tracings, an average vertical augmentation of the osseous segment was 4.2 mm at menton and that of the soft tissue menton was 4.0 mm. There was a high predictability of 1:0.94 between the amounts of hard versus soft tissue changes with surgery in the vertical plane. The position of the genial bone segment was stable immediately after surgery and soft tissue was not changed significantly from 1 month to 1 year after operation. Clinical and radiological follow-up results of the iliac bone graft showed normal bony union and were generally stable. CONCLUSIONS: VHA genioplasty using IBG is a reliable method for predicting hard and soft tissue changes and for maintaining postoperative soft tissue of the chin after surgery.