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A one-step hybrid bending/diffusion bonding process (HB/DBP) was developed for application to Ti-6Al-4V sheets to effectively improve buy-to-fly (BTF) ratio of aircraft parts, integrating sequential diffusion bonding followed by a bending process. The resulting bonding characteristics of these titanium alloy sheets were analyzed. Microstructural analysis and mechanical lap shear tests were performed to estimate the bonding quality. Additionally, bonding ratio, thickness strain, and shear strength were evaluated in relation to pressure under increasing temperature. When the applied pressure was lower than 0.5 MPa, early failure occurred at the joint of the specimens. However, when high pressure was applied, early failure occurred near the joint. To discuss the phenomenon, time-dependent viscoplastic material properties were characterized, and a numerical simulation analysis was performed. Viscoplastic deformation was observed around the bending area, which caused weakness around the bond under high-pressure conditions. A prototype of a Y-shaped heat shield was manufactured and the buy-to-fly ratio was effectively improved using the newly developed process. This study demonstrates the potential of applying the developed process for producing aircraft parts and the importance of viscoplastic behavior for the analysis of final product reliability.

In recent years, human-convenient smart wearable devices have attracted considerable attention as emerging applications in smart healthcare systems, soft robotics, and human-machine interfaces. In particular, resistive film heaters with mechanical flexibility and excellent mechanical and electrothermal performance have recently been widely explored for wearable thermotherapy applications. Here, we present a simple and efficient way of fabricating highly flexible and stretchable resistive film heaters based on a patterned silver nanowire (AgNW)/polymer composite structure. The AgNW/polymer composite electrodes were successfully prepared using a photolithographically patterned polymer mold based selective transfer of a AgNW percolation network. The photolithographic mold patterning process allows the heater fabrication to be precise and reproducible. The mesh-patterned AgNW/polymer composite heater exhibited the excellent electrothermal performance of ~46.7 oC at 3 V. This low-voltage operation is highly desirable in practical wearable device applications. Moreover, the AgNW/polymer heater can be stretched up to 20% without significant degradation in electrothermal performance thanks to its open-cell architecture, suggesting that the device can stably transfer heat to the skin after being attached to various body parts with curvilinear surfaces. The experimental results suggest that the mesh-structured AgNW/polymer composite heaters are highly feasible for use as a wearable thermotherapy tool in many emerging applications.

BACKGROUND: Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCs-laden acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury. METHODS: The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining. RESULTS: Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100β, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs. WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury. CONCLUSION: WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

Background and Aims: The utility of clinical information from esophagogastroduodenoscopy (EGD) reports has been limited because of its unstructured narrative format. We developed a natural language processing (NLP) pipeline that automatically extracts information about gastric diseases from unstructured EGD reports and demonstrated its applicability in clinical research. Methods: An NLP pipeline was developed using 2000 EGD and associated pathology reports that were retrieved from a single healthcare center. The pipeline extracted clinical information, including the presence, location, and size, for 10 gastric diseases from the EGD reports. It was validated with 1000 EGD reports by evaluating sensitivity, positive predictive value (PPV), accuracy, and F1 score. The pipeline was applied to 248,966 EGD reports from 2010–2019 to identify patient demographics and clinical information for 10 gastric diseases. Results: For gastritis information extraction, we achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.966, 0.972, 0.996, and 0.967, respectively. Other gastric diseases, such as ulcers, and neoplastic diseases achieved an overall sensitivity, PPV, accuracy, and F1 score of 0.975, 0.982, 0.999, and 0.978, respectively. The study of EGD data of over 10 years revealed the demographics of patients with gastric diseases by sex and age. In addition, the study identified the extent and locations of gastritis and other gastric diseases, respectively. Conclusions: We demonstrated the feasibility of the NLP pipeline providing an automated extraction of gastric disease information from EGD reports. Incorporating the pipeline can facilitate large-scale clinical research to better understand gastric diseases.

Evidence is growing that phthalate esters play an important role in the pathogenesis of estrogen-dependent gynecologic diseases, especially uterine fibroids. We aimed to investigate whether in vitro treatment with di-(2-ethylhexyl)-phthalate (DEHP) affects angiogenesis, proliferation, and apoptosis in uterine fibroids. To ascertain this, we evaluated vascular endothelial growth factor (VEGF) expression and AKT/ERT phosphorylation and compared the fibroid volume between nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice fed with and without DEHP. VEGF expression was measured using enzyme-linked immunosorbent assay, and AKT/ERK phosphorylation was analyzed by western blot analysis in human myometrial and fibroid cells. The volume of the fibroid tissues implanted to NOD/SCID mice was measured, and the expression of collagen type I protein, Ki-67, proliferating cell nuclear antigen, and B cell lymphoma 2 were analyzed using immunohistochemistry. We could see significant increases in VEGF expression and AKT phosphorylation in human myometrial and fibroid cells treated with DEHP. The volume of the fibroid tissues was significantly increased in NOD/SCID mice fed with DEHP, which was accompanied by increased expression of collagen type I and AKT phosphorylation. Taken together, these results suggest that exposure to phthalate esters may influence uterine fibroid pathogenesis by increasing VEGF and collagen expression and upregulating AKT phosphorylation.

Despite their extraordinary mechanosensitivities, most channel-like crack-based strain sensors are limited by their poor levels of stretchability and linearity. This work presents a simple yet efficient way of modulating the cracking structure of thin metal films on elastomers to facilitate the development of high-performance wearable strain sensors. A net-shaped crack structure based on a thin platinum (Pt) film can be produced by coating an elastomer surface with M13 bacteriophages (phages) and consequently engineering the surface strain upon stretching. This process produces a Pt-on-phage (PoP) strain sensor that simultaneously exhibits high levels of stretchability (24%), sensitivity (maximum gauge factor ≈ 845.6 for 20-24%), and linearity (

The discharge capacity of a tunnel drainage system generally decreases with time because of the hydraulic deterioration of the geotextile filter. Hydraulic deterioration restricts groundwater flow into a tunnel and increases water pressure resulting in detrimental effects on the tunnel lining. Hydraulic deterioration of tunnel drainage system is unique in terms of clogging materials, deterioration mechanism, and flow conditions. Current studies and models investigating the clogging mechanism and hydraulic deterioration are not directly applicable to the geotextile filter of the tunnel drainage system. In this study, a theoretical model of the hydraulic deterioration of tunnel geotextile filter has been proposed considering the mechanical and hydraulic behavior of blinding, clogging and squeezing. A parametric study was carried out to evaluate the performance of the model. An experimental study has been conducted to investigate the clogging behavior of the tunnel drainage system and validate the theoretical model. Several types of clogging materials were selected: cement-leaching calcium oxide, calcium carbonate, iron oxide, and bentonite. Agglutinated clogging was mainly observed during the short-term testing. The findings suggest that the in-plane permeability of the geotextile filter decreased by approximately 90%. The proposed model corroborated the experimental results.

Conventional mechanical crack-based strain sensors have high mechanosensitivity but suffer from limited stretchability and poor linearity. Here, we present a simple yet highly efficient strategy to enhance the strain-sensing performance of metal-based crack sensors based on platinum (Pt)/superaligned carbon nanotube (SACNT) hybrid conducting films. The proposed sensor is simply fabricated by transferring dry-spun SACNT films onto elastomer substrates and then sputtering Pt films. The SACNT underneath the Pt film endows the Pt crack sensors with large stretchability (e = 100%) and excellent linearity (R2 ≈ 0.996) while ensuring ultrahigh sensitivity (gauge factor ≈ 12 274) by modulating the cracking structure in the Pt film so that the cracked Pt parts can be bridged upon stretching even at high strains. In addition, the sensor response is found to be quite fast (≈257.7 ms) and stable even under long-term operation (2000 cycles at 50% strain). Based on their excellent strain-sensing performance and mechanical flexibility, the sensors are demonstrated to detect a wide range of human motions in real time. Moreover, two single sensors can be successfully assembled in a cross shape to detect complex multiaxial strains.

Damage to normal tissue can occur over a long period after cancer radiotherapy. Free radical by radiation can initiate or accelerate chronic inflammation, which can lead to atherosclerosis. However, the underlying mechanisms remain unclear. Vascular smooth muscle cells (VSMCs) proliferate in response to JAK/STAT3 signalling. C-reactive protein (CRP) can induce VSMCs apoptosis via triggering NADPH oxidase (NOX). Apoptotic VSMCs promote instability and inflammation of atherosclerotic lesions. Herein, we identified a VSMCs that switched from proliferation to apoptosis through was enhanced by radiation-induced CRP. NOX inhibition using lentiviral sh-p22

Superhydrophobic surfaces with mechanical compliance and optical visibility open up new possibilities in practical applications. This work presents a simple, fast, and cost-effective route to fabricate highly flexible and transparent superhydrophobic films with hierarchical surface morphology. Two-tiered polymeric surface structures are readily obtained by a one-step photopatterning approach in conjunction with a roughened sandpaper template. The hierarchical superhydrophobic polymer (HSP) films show excellent wetting properties (static contact angle of >172° and contact angle hysteresis of 84% at 550 nm), and enhanced resistance to water drop impact. In addition, the HSP films exhibit high resistance to repeated bending and pressing deformations (5000 cycles), while stably maintaining their superhydrophobicity. The practical utility of the HSP film is successfully demonstrated through self-cleaning, anti-fogging, and water-jet impact tests.

The palatine tonsils (hereinafter referred to as "tonsils") serve as a reservoir for viral infections and play roles in the immune system's first line of defense. The aims of this study were to establish tonsil epithelial cell-derived organoids and examine their feasibility as an ex vivo model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The tonsil organoids successfully recapitulated the key characteristics of the tonsil epithelium, including cellular composition, histologic properties, and biomarker distribution. Notably, the basal layer cells of the organoids express molecules essential for SARS-CoV-2 entry, such as angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and furin, being susceptible to the viral infection. Changes in the gene expression profile in tonsil organoids revealed that 395 genes associated with oncostatin M signaling and lipid metabolism were highly upregulated within 72 h after SARS-CoV-2 infection. Notably, remdesivir suppressed the viral RNA copy number in organoid culture supernatants and intracellular viral protein levels in a dose-dependent manner. Here, we suggest that tonsil epithelial organoids could provide a preclinical and translational research platform for investigating SARS-CoV-2 infectivity and transmissibility or for evaluating antiviral candidates.

SUMMARYPalatine tonsil (hereinafter referred to as “tonsil”) plays role in the immune system’s first line of defense against foreign pathogens. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide pandemic since the infection was first reported in China in December 2019. The aim of this study was to establish tonsil epithelial cell-derived organoids and to examine their feasibility as anex vivomodel for SARS-CoV-2 infection. Using an optimized protocol, we achieved 3D tonsil organoid culture from human tonsil tissue that reflects the distinctive characteristics of the tonsil epithelium, such as its cellular composition, histologic properties, and molecular biological features. Notably, we verified that SARS-CoV-2 can infect tonsil organoids with a robust replication efficiency. Furthermore, treatment with remdesivir, an antiviral agent, effectively protected them from viral infection. Therefore, tonsil organoids could be available for investigation of SARS-CoV-2 infection-mediated pathology and for preclinical screening of novel antiviral drug candidates.One-sentence SummaryThis study established tonsil epithelial cell-derived organoids and demonstrated their feasibility as anex vivomodel for SARS-CoV-2 infection.

This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.

International audience; Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small-and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

Adjusting the font size is a function of the smartphone for improving readability. This smartphone is easier to use than other function but is less useful due to the psychological factors experienced by users, such as annoyance or fear of malfunction. Adjusting the font size is difficult when you are on the move or cannot use both hands to hold the smartphone. Therefore, we need a system that can automatically adjust the font size under any circumstances to improve readability. In this paper, we implement a system, in which the font size is automatically adjusted according to the distance between the user and the smartphone, without additional device operations. By automatically adjusting the font size, this system can increase readability while reducing difficulties in operation.

Ignition of nanoenergetic materials (nEMs) has great potential for various portable and disposable actuator applications due to the unique ability to release pressure in a controllable manner. The development of highly efficient low-power igniters is very important in this context. Here we present a focused-laser-assisted nEMs igniter that can be remotely operated at low power with a portable laser pointer. The proposed optical igniter is monolithically integrated with a polymeric lens and prepared by a very simple, fast, and reproducible single-step soft-lithographic replication process using polydimethylsiloxane (PDMS). The polymeric lens plays a crucial role in greatly enhancing the laser power density on a target area by efficiently concentrating the incident laser beam, generating thermal energy enough to ignite nEMs. A pressure-driven membrane actuator is fabricated by integrating a thin PDMS membrane to the nEMs-coated optical igniter, and the actuation behavior is characterized in response to pressure released by nEMs ignition with different numbers of nEMs coats. Finally, the pressure-driven membrane actuator is demonstrated in an alarm switch to trigger stable operation of an electric buzzer with a blinking light-emitting diode as a potential application.

Recent efforts to develop stretchable resistive heaters open up the possibility for their use in wearable thermotherapy applications. Such heaters should have high electrothermal performance and stability to be used practically, and the fabrication must be simple, economic, reproducible, and scalable. Here we present a simple yet highly efficient way of producing high-performance stretchable heaters, which is based on a facile kirigami pattering (the art of cutting and folding paper) of a highly conductive paper for practical wearable thermotherapy. The resulting kirigami heater exhibits high heating performance at low voltage (40 °C at 1.2 V) and fast thermal response (60 s). The simple kirigami patterning approach enables the heater to be extremely stretchable (400%) while stably retaining its excellent performance. Furthermore, the heater shows the uniform spatial distribution of heat over the whole heating area and is highly durable (1000 cycles at 300% strain). The heater attached to curvilinear body parts shows stable heating performance even under large motions while maintaining intimate conformal contact with the skin thanks to the high stretchability and sufficient restoring force. The usability of the heater as a wearable thermotherapy device is demonstrated by increased blood flow at the wrist during operation.

While micropiles are used in many geotechnical projects, as ground reinforcement rather than as structural elements, field engineers have reported that the bearing capacity of micropiled rafts greatly exceeds the range of common ground reinforcement. This is known to be due to the confining effects of micropiles from the interaction between the ground and the micropiles, which extends the failure area of the ground significantly. Utilizing micropiles as ground reinforcement can excessively underestimate the structural contribution of the footing in a micropiled-raft system to the bearing capacity. This study investigates the support characteristics of a micropiled raft through model tests and a numerical analysis. The support behavior of the micropiled raft is evaluated for various conditions, such as soil type, pile length, and installation angle. It is found that the micropiles modify the failure behavior of the ground considerably, and that the bearing resistance can be enhanced by considering the appropriate failure mode, installation angle, and pile length.

Although several studies have focused on the oncologic impact of the preoperative prognostic nutritional index (PNI), there is no study correlating the preoperative PNI changes with the oncologic outcome of resected pancreatic cancer following neoadjuvant chemotherapy (NAC).We retrospectively analyzed 107 pancreatic ductal adenocarcinoma patients who underwent NAC followed by surgical resection. ΔPNI was defined as post-NAC PNI subtracted from pre-NAC PNI. Patients were divided into high (≥-1.94, n = 54) and low ΔPNI groups (-1.94, n = 53). Long-term oncologic outcomes, such as overall survival (OS) and disease-free survival (DFS), were compared. Univariate and multivariate analysis were used to identify independent prognostic factors.The high ΔPNI group correlated with lower pre-NAC PNI (46.96 ± 4.68 vs. 51.77 ± 5.63, p 0.001) and higher post-NAC PNI (50.05 ± 4.80 vs. 42.56 ± 7.44, p 0.001) more than the low ΔPNI group. The high ΔPNI group was also associated with longer OS compared with the low ΔPNI group (mean OS: 63.97 months [95% CI: 49.95-77.99] vs. 41.16 months [95% CI: 27.66-54.66], p = 0.003); there was no significant difference in DFS (p 0.05). Multivariate analysis revealed that low ΔPNI was an independent risk factor for OS (HR, 3.516; 95% CI, 1.885-6.558; p 0.001), but not for DFS (p 0.05).Low ΔPNI (-1.94) was an independent risk factor for the overall survival of resected pancreatic cancer patients following NAC. In the preoperative setting, improving the PNI can better the long-term oncologic outcome of this condition.

In the event of a mass casualty radiation scenario, biodosimetry has the potential to quantify individual exposures for triaging and providing dose-appropriate medical intervention. Structural maintenance of chromosomes 1 (SMC1) is phosphorylated in response to ionizing radiation. The goal of this study was to develop a new biodosimetry method using SMC1 phosphorylation as a measure of exposure to radiation. In the initial experiments, two normal human cell lines (WI-38VA-13 and HaCaT) and four lymphoblastoid cell lines were irradiated, and the levels of SMC1 phosphorylation at Ser-360 and Ser-957 were assessed using Western blotting. Subsequently, similar experiments were performed using peripheral blood mononuclear cells (PBMCs) obtained from 20 healthy adults. Phosphorylation of SMC1 at Ser-957 and Ser-360 was increased by exposure in a dose-dependent manner, peaked at 1-3 h postirradiation and then decreased gradually. Ser-360 was identified as a new phosphorylation site and was more sensitive to radiation than Ser-957, especially at doses below 1 Gy. Our results demonstrate a robust ex vivo response of phospho-SMC1-(Ser-360) to ionizing radiation in human PBMCs. Detection of phosphorylation at Ser-360 in SMC1 could be used as a marker of radiation exposure. Our findings suggest that it is feasible to measure blood cell-based changes in the phosphorylation level of a protein as an ex vivo radiation exposure detection method, even after low-dose exposure.

Kang-Hyun Kim,1 Tai Sun Park,2,3 You-Sun Kim,1,3 Jae Seung Lee,2,3 Yeon-Mok Oh,2,3 Sang-Do Lee,2,3 Sei Won Lee2,3 1Asan Institute for Life Sciences, 2Department of Pulmonology and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, 3Department of Pulmonology and Critical Care Medicine, University of Ulsan College of Medicine, Seoul, Republicof Korea Purpose: Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration.Materials and methods: C57BL/6 mice, 8weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4weeks with poly(I:C) or to smoking only for 24weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid.Results: Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking.Conclusion: RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. Keywords: resolvin D1, COPD, emphysema

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called "priming" factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK(p42/44) and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients.

Micropatterning of conductive nanomaterials (CNs) is one of the most important issues in developing practical stretchable devices. This work presents a systematic micropatterning of CNs by simply combining a well-established lift-off process and facile spray coating of CNs. Various micropatterns made of a silver nanowire (AgNW) percolation network are precisely and stably defined in a large-area elastomeric substrate. Based on systematic lift-off micropatterning coupled with interlayer alignment techniques, resistive and capacitive stretchable sensors are fabricated in a precise and reproducible manner. The usability of the approach is also experimentally confirmed by successfully demonstrating a motion-sensing glove using stretchable resistive strain sensors and a 16 × 16 elastic capacitive tactile sensor array.

Giant stretchability of an elastic conductor can potentially extend its application scope in the emerging field of stretchable electronics. We present a new class of extremely stretchable conductors based on a hierarchically-structured (HS) metal nanowire network that can be simply fabricated by a prestraining technique with a micro-prism-arrayed elastomeric substrate. The unique architecture of the HS conductor with aligned metal nanowires on a sloped surface of a micro-prism structure makes it possible to achieve ultra-stretchability of higher than 700% while ensuring electrical and mechanical robustness. The HS stretchable conductor shows highly stable and reversible electrical performance even under high (∼750%) and repetitive (100 cycle) strains.

Stem cell (SC) therapy has become a potential treatment modality for pulmonary artery hypertension (PAH), but the efficacy of human SC and priming effects have not yet been established. The mobilization and homing of hematopoietic stem cells (HSCs) are modulated by priming factors that include a bioactive lipid, sphingosine-1-phosphate (S1P), which stimulates CXCR4 receptor kinase signaling. Here, we show that priming human mesenchymal stem cells (MSCs) with S1P enhances their therapeutic efficacy in PAH. Human MSCs, similar to HSCs, showed stronger chemoattraction to S1P in transwell assays. Concomitantly, MSCs treated with 0.2 μM S1P showed increased phosphorylation of both MAPKp42/44 and AKT protein compared with nonprimed MSCs. Furthermore, S1P-primed MSCs potentiated colony forming unit-fibroblast, anti-inflammatory, and angiogenic activities of MSCs in culture. In a PAH animal model induced by subcutaneously injected monocrotaline, administration of human cord blood-derived MSCs (hCB-MSCs) or S1P-primed cells significantly attenuated the elevated right ventricular systolic pressure. Notably, S1P-primed CB-MSCs, but not unprimed hCB-MSCs, also elicited a significant reduction in the right ventricular weight ratio and pulmonary vascular wall thickness. S1P-primed MSCs enhanced the expression of several genes responsible for stem cell trafficking and angiogenesis, increasing the density of blood vessels in the damaged lungs. Thus, this study demonstrates that human MSCs have potential utility for the treatment of PAH, and that S1P priming increases the effects of SC therapy by enhancing cardiac and vascular remodeling. By optimizing this protocol in future studies, SC therapy might form a basis for clinical trials to treat human PAH.

In order to design an advanced composite materials drainage pipe structures for an undersea tunnel, mechanical properties for the lamina types of the structural member must be predetermined. It is also reported that the size effect of the specimen is significant. In this study the tensile tests for the lamina types of the structural member are conducted at the room temperature () and the seawater temperature (). In addition, the mechanical properties are predicted by theory based on the rule of mixtures and elasticity solution technique. The predicted mechanical properties are compared with test results obtained by a test method. In the design of an advanced composite materials drainage pipe structural members for an undersea tunnel, the used mechanical properties must be applied at the room temperature with considering the modified factors. These are to be offered the datum for the design an advanced composite materials drainage pipe structures for an undersea tunnel.

Next-generation stretchable optoelectronics require functional electric conductors with mechanical stretchability and optical transparency. We present a new class of highly stretchable and transparent conductors based on silver nanowire (AgNW) percolation micro-grids embedded in an elastomeric substrate. These are prepared by simple spray-coating and subsequent adhesive-tape-assisted contact-removal of AgNWs. The synergistic combination of the percolated NWs and regular micro-grid geometry in an integrated form makes it possible to achieve uniform, reproducible, and predictable performance of the resulting AgNW micro-grids and ensure good stretchability. The fabricated device shows superior optoelectronic performance with a sheet resistance of 26.1 Ω sq−1 and an optical transmittance of 85.8%. In addition, the device can reversibly accommodate various mechanical deformations, such as stretching, bending, and twisting.

Study question Does interleukin-32 (IL-32) play a role in the pathogenesis of endometriosis? Summary answer IL-32 might be involved in the pathogenesis of endometriosis through increased viability, proliferation and invasion of endometrial cells. What is known already Endometriosis is characterized as a chronic inflammatory disease and several proinflammatory cytokines are suggested to be involved in its pathogenesis and pathophysiology. IL-32, recognized as a new proinflammatory cytokine and a strong inducer of other proinflammatory cytokines, has been shown to serve as a key modulator in several chronic inflammatory diseases. Study design, size, duration This study included comparison of IL-32 levels in the peritoneal fluids between women with and without endometriosis, in-vitro experiments using Ishikawa cells and endometrial stromal cells (ESCs), and experiments on IL-32 transgenic mice and wild-type mice with induced endometriosis. Participants/materials, setting, methods IL-32 levels in the peritoneal fluids were measured using enzyme-linked immunosorbent assays. Cell viability, expression of proliferating cell nuclear antigen (PCNA), and cellular invasiveness were analyzed following in-vitro treatment of Ishikawa cells and ESCs with recombinant IL-32 alpha (α) and gamma (γ). Ectopic endometriotic lesions were compared between IL-32 transgenic mice and wild-type mice after autologous endometrial transplantation with immunohistochemistry for Ki-67 antigen and PCNA. Main results and the role of chance The peritoneal fluid concentration of IL-32 was significantly higher in patients with advanced stage endometriosis compared with the controls. In-vitro treatment with IL-32 α and γ caused significant increases in cellular viability, PCNA expression, and invasiveness in Ishikawa cells and ESCs. The IL-32 transgenic mice had a significantly larger size of the ectopic endometrial lesions with higher expression of Ki-67 antigen and PCNA compared with wild-type mice. Large scale data N/A. Limitations, reasons for caution It is still unclear whether IL-32 is a main regulator, or one of several downstream proinflammatory cytokines, causing establishment and/or progression of endometriosis. Wider implications of the findings Further investigation on IL-32 signaling pathways may contribute to development a more effective treatment of endometriosis. Study funding/competing interest(s) This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI16C1682). None of the authors has anything to disclose.

This work presents a new template-assisted fabrication method to obtain stretchable metal grids for high-performance stretchable transparent conducting electrodes (TCEs). Readily accessible metal woven mesh (MWM) is used as a template to make the fabrication process simple, cost-effective, reproducible, and potentially scalable by combining it with silver nanowire (AgNW) coating and elastomer filling processes. Stretchable TCEs are made with the AgNW-coated MWM and show remarkable optoelectronic performance with a sheet resistance of ∼3.2 Ω/sq and optical transmittance of >80%, large maximum stretchability of 40%, and electrical and mechanical robustness even under repeated stretching and bending deformations (1000 cycles). The device is demonstrated in a highly flexible touch screen panel that can operate well even in a bent state.

Wearable pressure sensors are crucial building blocks for potential applications in real-time health monitoring, artificial electronic skins, and human-to-machine interfaces. Here we present a highly sensitive, simple-architectured wearable resistive pressure sensor based on highly compliant yet robust carbon composite conductors made of a vertically aligned carbon nanotube (VACNT) forest embedded in a polydimethylsiloxane (PDMS) matrix with irregular surface morphology. A roughened surface of the VACNT/PDMS composite conductor is simply formed using a sandblasted silicon master in a low-cost and potentially scalable manner and plays an important role in improving the sensitivity of resistive pressure sensor. After assembling two of the roughened composite conductors, our sensor shows considerable pressure sensitivity of ∼0.3 kPa–1 up to 0.7 kPa as well as stable steady-state responses under various pressures, a wide detectable range of up to 5 kPa before saturation, a relatively fast response time of ∼16...

In double-lined tunnels, geotextiles are installed between shotcrete and concrete linings to drain ground water that is in the circumferential boundary of the tunnels. During the concrete lining placement, the geotextile often experiences pressures from young concrete on the curved and rough shotcrete surfaces. The pressures are transferred through a waterproof membrane, and act in the normal direction to the curved shotcrete face. The geotextile flow behavior under these conditions cannot be represented by standard geotextile permeability tests. Instead, it requires specially designed performance tests that consider field conditions. A new device to evaluate the permeability of the geotextile in pressurized curved flow channels is proposed; it adopts a flexible loading system and a curved and rough model plate. Testing of geotextiles used for tunnel drainage systems, using the proposed arrangement, shows that the effects of the tortuousity of the flow in pressurized channels affects significantly the geotextile permeability.

The point-based complex event processing handled an instantaneous event by using one time stamp in each event. However, the activity period of the event plays the important role in the field which is the same as the finance, multimedia, medicine, and meteorology. The point-based event is insufficient for expressing the complex temporal relationship in this field. In the application field of the real-time world, the event has the period. The events more than two kinds can be temporally overlapped. In addition, one event can include the other event. The relation about the events of kind of these can not be successive like the point-based event. This thesis designs and implements the method detecting the patterns of the complex event by using the interval-based events. The interval-based events can express the overlapping relation between events. Furthermore, it can include the others. By using the end point of beginning and end point of the termination, the operator of interval-based events shows the interval-based events. It expresses the sequence of the interval-based events and can detect the complex event patterns. This thesis proposes the algorithm using the active instance stack in order to raise efficiency of detection of the complex event patterns. When comprising the event sequence, this thesis applies the window push down technique in order to reduce the number of intermediate results. It raises the utility factor of the running time and memory.

High sensitivity and high stretchability are two conflicting characteristics that are difficult to achieve simultaneously in elastic strain sensors. A highly sensitive and stretchable strain sensor comprising a microstructured metal nanowire (mNW)/elastomer composite film is presented. The surface structure is easily prepared by combining an mNW coating and soft-lithographic replication processes in a simple and reproducible manner. The densely packed microprism-array architecture of the composite film leads to a large morphological change in the mNW percolation network by efficiently concentrating the strain in the valley regions upon stretching. Meanwhile, the percolation network comprising mNWs with a high aspect ratio is stable enough to prevent electrical failure, even under high strains. This enables the sensor to simultaneously satisfy high sensitivity (gauge factor ≈81 at >130% strain) and high stretchability (150%) while ensuring long-term reliability (10 000 cycles at 150% strain). The sensor can also detect strain induced by bending and pressure, thus demonstrating its potential as a versatile sensing tool. The sensor is successfully utilized to monitor a wide range of human motions in real time. Furthermore, the unique sensing mechanism is easily extended to detect more complex multiaxial strains by optimizing the surface morphology of the device.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease, and bacterial infection plays a role in its pathogenesis. Bacteria secrete nanometer-sized extracellular vesicles (EVs), which may induce more immune dysfunction and inflammation than the bacteria themselves. We hypothesized that the microbiome of lung EVs might have distinct characteristics depending on the presence of COPD and smoking status. We analyzed and compared the microbiomes of 13 nonsmokers with normal spirometry, 13 smokers with normal spirometry (healthy smokers) and 13 patients with COPD by using 16S ribosomal RNA gene sequencing of surgical lung tissue and lung EVs. Subjects were matched for age and sex in all groups and for smoking levels in the COPD and healthy smoker groups. Each group included 12 men and 1 woman with the same mean age of 65.5 years. In all groups, EVs consistently showed more operational taxonomic units (OTUs) than lung tissue. In the healthy smoker and COPD groups, EVs had a higher Shannon index and a lower Simpson index than lung tissue and this trend was more prominent in the COPD group. Principal component analysis (PCA) showed clusters based on sample type rather than participants' clinical characteristics. Stenotrophomonas, Propionibacterium and Alicyclobacillus were the most commonly found genera. Firmicutes were highly present in the EVs of the COPD group compared with other samples or groups. Our analysis of the lung microbiome revealed that the bacterial communities present in the EVs and in the COPD group possessed distinct characteristics with differences in the OTUs, diversity indexes and PCA clustering.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease that responds to the interplay of environmental, immunological, and genetic factors. To explore the effect of Vaccinium uliginosum (VU) extract on AD, we orally administrated VU total water extract to AD-induced NC/Nga mice. VU extract reduced AD-like skin lesions, ear thickness, and the frequency of scratching episodes in a time-dependent manner. VU also suppressed the levels of IgE and histamine and the ratio of IgG1/IgG2a in the serum of AD-induced NC/Nga mice. VU administration resulted in the reduction of splenic cytokine production, epidermal thickening, and the infiltration of eosinophils, mast cells, and degranulated mast cells induced by 2,4-dinitrochlorobenzene (DNCB). In addition, VU significantly reduced the mRNA expression of chemokine ligands in dorsal skin. Total water extract and subfractions of VU inhibited interleukin (IL)-4 production in splenocytes, suggesting that VU total extract has a Th2 cytokine modulating effect. These results suggest that the VU total water extract could be a candidate therapeutic agent for the treatment of AD through an immunoregulatory effect.