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Abstract Patients with lung adenocarcinoma who have never smoked (NSLA) and lack key driver mutations, such as those in the EGFR and ALK genes, face limited options for targeted therapies. They also tend to have poorer outcomes with immune checkpoint inhibitors than lung cancer patients who have a history of smoking. The proteogenomic profile of nonsmoking lung adenocarcinoma patients without these oncogenic driver mutations is poorly understood, which complicates the precise molecular classification of these cancers and highlights a significant area of unmet clinical need. This study analyzed the genome, transcriptome, and LC‒MS/MS-TMT-driven proteome data of tumors obtained from 99 Korean never-smoker lung adenocarcinoma patients. NSLA tumors without EGFR or ALK driver oncogenes were classified into four proteogenomic subgroups: proliferation, angiogenesis, immune, and metabolism subgroups. These 4 molecular subgroups were strongly associated with distinct clinical outcomes. The proliferation and angiogenesis subtypes were associated with a poorer prognosis, while the immune subtype was associated with the most favorable outcome, which was validated in an external lung cancer dataset. Genomic-wide impacts were analyzed, and significant correlations were found between copy number alterations and both the transcriptome and proteome for several genes, with enrichment in the ERBB, neurotrophin, insulin, and MAPK signaling pathways. Proteogenomic analyses suggested several targetable genes and proteins, including CDKs and ATR, as potential therapeutic targets in the proliferation subgroup. Upregulated cytokines, such as CCL5 and CXCL13, in the immune subgroup may serve as potential targets for combination immunotherapy. Our comprehensive proteogenomic analysis revealed the molecular subtypes of EGFR- and ALK-wild-type NSLA with significant unmet clinical needs.

Abstract Gaseous and particulate 21 PAHs were monitored at a residential site in Ulsan, South Korea, over three seasons (December 2013–August 2014). The mean concentrations of Σ21 PAHs were highest in winter (16.2 ± 8.2 ng/m3), followed by spring (8.37 ± 4.53 ng/m3) and summer (6.23 ± 2.53 ng/m3). The mean gaseous concentration of Σ21 PAHs (7.39 ± 4.39 ng/m3) was 2.7 times higher than that of particulate PAHs (2.70 ± 3.38 ng/m3). To identify the sources of PAHs (both types of sources and their areas), diagnostic ratios, principal component analysis, and concentration-weighted trajectory (CWT) were used. The results showed that pyrogenic sources (e.g., coal combustion) were the primary emission sources of PAHs in winter and spring. In summer, the influence of both coal and heavy oil combustion was dominant, suggesting that PAHs could be transported from industrial areas of Ulsan (e.g., petrochemical and nonferrous industrial complexes) by seasonal winds. Regarding emission source areas, the CWT analysis revealed that in winter and spring, PAHs in Ulsan could be attributed to emissions from regional areas, e.g., China and North Korea. The PAH concentrations were also used to assess the health risks associated with the inhalation of these compounds for adults aged 18–70. The results showed that the cancer risks from Σ19 PAHs and Σ13 PAHs did not exceed the guideline set by the US EPA (10−6), indicating no cancer risks for this target group. However, it is worth noting that certain PAHs, which are not listed as priority PAHs by the US EPA, make significant contributions to the benzo[a]pyrene equivalent and the associated cancer risks. Therefore, it is necessary to investigate not only the priority PAHs but also other PAH species to fully evaluate their effect on human health.

Abstract Protein arginine methyltransferases (PRMTs) modulate diverse cellular processes, including stress responses. The present study explored the role of Prmt7 in protecting against menopause-associated cardiomyopathy. Mice with cardiac-specific Prmt7 ablation (cKO) exhibited sex-specific cardiomyopathy. Male cKO mice exhibited impaired cardiac function, myocardial hypertrophy, and interstitial fibrosis associated with increased oxidative stress. Interestingly, female cKO mice predominantly exhibited comparable phenotypes only after menopause or ovariectomy (OVX). Prmt7 inhibition in cardiomyocytes exacerbated doxorubicin (DOX)-induced oxidative stress and DNA double-strand breaks, along with apoptosis-related protein expression. Treatment with 17β-estradiol (E2) attenuated the DOX-induced decrease in Prmt7 expression in cardiomyocytes, and Prmt7 depletion abrogated the protective effect of E2 against DOX-induced cardiotoxicity. Transcriptome analysis of ovariectomized wild-type (WT) or cKO hearts and mechanical analysis of Prmt7-deficient cardiomyocytes demonstrated that Prmt7 is required for the control of the JAK/STAT signaling pathway by regulating the expression of suppressor of cytokine signaling 3 (Socs3), which is a negative feedback inhibitor of the JAK/STAT signaling pathway. These data indicate that Prmt7 has a sex-specific cardioprotective effect by regulating the JAK/STAT signaling pathway and, ultimately, may be a potential therapeutic tool for heart failure treatment depending on sex.

We integrated transparent antireflective coatings and transparent electrodes onto flexible colorless polyimide (CPI) substrates to fabricate high-performance flexible perovskite solar cells. Multifunctional PPFC/CPI/IGTO substrates were fabricated by sputtering the optimal plasma-polymerized fluorocarbon (PPFC) antireflective coating and InGaTiO (IGTO) electrode films on both sides of the CPI substrate. By applying PPFC with a low refractive index (1.38) as an antireflective coating, the transparency of the PPFC/CPI/IGTO substrate increased by an additional 1.2%. In addition, owing to the amorphous characteristics of the PPFC and IGTO layers, the PPFC/CPI/IGTO substrate showed constant sheet resistance and transmittance change even after 10,000 cycles during the bending tests. The flexible perovskite solar cells, fabricated on the PPFC/CPI/IGTO substrate, exhibited an increase in current density of 1.48 mA/cm2 after the deposition of the PPFC antireflective coating. These results confirmed that the PPFC/CPI/IGTO substrate was durable against high-temperature treatment, flexible, and exhibited excellent electrical characteristics. This enhanced the efficiency and durability of the flexible perovskite solar cells. Moreover, the hydrophobic PPFC layer allowed the self-cleaning of inflexible perovskite solar cells. Given these attributes, the PPFC/CPI/IGTO structure has been recognized as a good choice for multifunctional substrates of flexible perovskite solar cells, presenting the potential for enhancing performance.

Abstract Since its initial description 35 years ago as an inducible molecule expressed in cytotoxic and helper T cells, 4-1BB has emerged as a crucial receptor in T-cell-mediated immune functions. Numerous studies have demonstrated the involvement of 4-1BB in infection and tumor immunity. However, the clinical development of 4-1BB agonist antibodies has been impeded by the occurrence of strong adverse events, notably hepatotoxicity, even though these antibodies have exhibited tremendous promise in in vivo tumor models. Efforts are currently underway to develop a new generation of agonist antibodies and recombinant proteins with modified effector functions that can harness the potent T-cell modulation properties of 4-1BB while mitigating adverse effects. In this review, we briefly examine the role of 4-1BB in T-cell biology, explore its clinical applications, and discuss future prospects in the field of 4-1BB agonist immunotherapy.

Objectives Cigarette smoking is an important factor in human exposure to polycyclic aromatic hydrocarbons (PAHs). Machine-smoking methods have been devised to evaluate inhalation exposure to mainstream cigarette smoke. However, there have been only a few studies that have employed these methods for PAH monitoring in Korea. Methods Total particulate matter samples were collected from the mainstream smoke of five different cigarette types using the ISO 3308 standard smoking method. The samples were analyzed for 16 PAHs using a gas chromatograph/mass spectrometer (GC/MS) following extraction and clean-up procedures. Results and Discussion The 16 PAH levels of cigarette samples ranged from 87.1 ng/cig to 247.4 ng/cig with an average of 135.4 ng/cig. The average fractions of PAHs classified by the number of rings were as follows: 15% (2 rings), 37% (3 rings), 43% (4 rings), 4% (5 rings), and 1% (6 rings). Diagnostic ratios suggested that the characteristics of PAH pollution in mainstream cigarette smoke were similar to those of biomass burning but different from those of ambient air. The carcinogenic risks of PAHs exceeded the risk threshold of the US EPA (1.0E-06) for the 10%, 30%, and 20% exposure groups of adult males, adult females, and all adults, respectively. Conclusion This study highlights the significance of mainstream cigarette smoke in examining human inhalation exposure to PAHs and carcinogenic risks, which are primarily influenced by cigarette smoking rather than ambient air. These findings can contribute to a comprehensive assessment of inhalation exposure to PAHs and provide guidance for the development of environmental health policies aimed at reducing such exposure.

Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

[This corrects the article DOI: 10.1371/journal.pone.0083734.].

Abstract This study aims to analyze the sensitivity of volatile organic compounds (VOCs) to ambient concentrations of fine particles (PM2.5) in the representative industrial city of Ulsan, Korea. For the calculation of sensitivity coefficients between VOCs and PM2.5 (SVOCs-PM2.5), PM2.5 data were obtained from an air quality monitoring station, and their corresponding 6-h average concentrations of VOCs (alkanes, alkenes, aromatics, and total VOCs) were measured at the Yeongnam intensive air monitoring station. The air monitoring period was divided into the warm-hot season (May–October 2020) and the cold season (November 2020–January 2021). The sensitivity coefficients in the low pollution period of PM2.5 (5 35 μg/m3, than other VOC groups. The result of this study can be a basis for establishing PM2.5 management plans in industrial cities with large VOC emissions.

Abstract This article reports on the charge transport characteristics across the potential barrier generated by a local dual‐gate modulation at the surface of p‐doped graphene via surface contact on a fluorocarbon (CF) thin film. Owing to simple physical contact, the strong electron affinity of the fluorine atoms in CF stably increases the hole density of graphene, which leads to a massive p‐doping effect in graphene. Then, potential barrier height can be generated and modulated across the channel by forming a local dual‐gate device structure. Different gate biases in dual‐gate operation can split electrical characteristics of a single graphene into highly conductive region and region of sparse charge density, creating large chemical potential difference at the boundary between the two which determines the value of barrier height. Moreover, the device characteristics follow a simple model of the metal–semiconductor junction well in addition to the effect of charge concentration discrepancy in graphene. These results reveal that it is possible to create an ideal and controllable potential barrier composed of a single material using the highly doped graphene with the local dual‐gate structure.

Elucidation of the interplay between viruses and host cells is crucial for taming viruses to benefit human health. Cancer therapy using adenovirus, called oncolytic virotherapy, is a promising treatment option but is not robust in all patients. In addition, inefficient replication of human adenovirus in mouse hampered the development of an in vivo model for preclinical evaluation of therapeutically engineered adenovirus. nc886 is a human non-coding RNA that suppresses Protein Kinase R (PKR), an antiviral protein. In this study, we have found that nc886 greatly promotes adenoviral gene expression and replication. Remarkably, the stimulatory effect of nc886 is not dependent on its function to inhibit PKR. Rather, nc886 facilitates the nuclear entry of adenovirus via modulating the kinesin pathway. nc886 is not conserved in mouse and, when xenogeneically expressed in mouse cells, promotes adenovirus replication. Our investigation has discovered a novel mechanism of how a host ncRNA plays a pro-adenoviral role. Given that nc886 expression is silenced in a subset of cancer cells, our study highlights that oncolytic virotherapy might be inefficient in those cells. Furthermore, our findings open future possibilities of harnessing nc886 to improve the efficacy of oncolytic adenovirus and to construct nc886-expressing transgenic mice as an animal model.

Blood pressure measurement is required to monitor the cardiovascular state of a person, and it is commonly conducted in a noninvasive way using oscillometry-based blood pressure monitors (BPM). Blood pressure can be estimated by analyzing the oscillometric waveform (OMW) in the BPM, and many methods have been examined to increase their estimation accuracy. In this study, we proposed a new method that enhances estimation accuracy and requires no external user information, such as age and gender, in the test phase. In the method, the entire OMW was considered as an input to reduce information loss via feature extraction, and convolutional neural networks were utilized to effectively analyze the high-dimensional input. Additionally, the proposed method included a novel ensemble method to further increase the estimation accuracy. The performance of the proposed method was evaluated and compared with other studies via subject-independent tests considering real situations in which it is difficult to obtain preliminary information on a test subject. Data from 64 subjects were used in the test. The mean absolute error of the proposed method was 3.12 and 3.98 mmHg for systolic and diastolic blood pressure, respectively, which was superior to those reported in other studies conducted in similar conditions. Individuals can measure their blood pressure with higher precision using the proposed method with improved estimation performance. This can aid in reducing the risk of cardiovascular diseases.

CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization. As an in vivo model, C57BL/6 mice were subcutaneously injected with MEER/CD200High cells, CD200-overexpressing mouse HNSCC cells. Adenovirus-expressing sCD200R1-Ig (Ad5sCD200R1) was designed, and its effect was tested. Components in the tumor-immune microenvironment (TIME) were quantified using flow cytometry. CD200 promoted tumor growth and induced the expression of immune-related genes, especially macrophage colony-stimulating factor (M-CSF). Interestingly, CD200 induced M2-like polarization both in vitro and in vivo. Consequently, CD200 recruited more regulatory T (Treg) cells and fewer CD8+ effector T cells. These effects were effectively abolished by local injection of Ad5sCD200R1. These protumor effects of CD200 were driven through the β-catenin/NF-κB/M-CSF axis. CD200 upregulated PD-L1, and the combined targeting of CD200 and PD-1 thus showed synergy. The immune checkpoint CD200 upregulated immune-related genes through β-catenin signaling, reprogrammed the TIME, and exerted protumor effects. Ad5sCD200R1 injection could be an effective targeted strategy to enhance antitumor immunoediting.

Accurate evaluation of thermo-fluid dynamic characteristics in tanks is critically important for designing liquid hydrogen tanks for small-scale hydrogen liquefiers to minimize heat leakage into the liquid and ullage. Due to the high costs, most future liquid hydrogen storage tank designs will have to rely on predictive computational models for minimizing pressurization and heat leakage. Therefore, in this study, to improve the storage efficiency of a small-scale hydrogen liquefier, a three-dimensional CFD model that can predict the boil-off rate and the thermo-fluid characteristics due to heat penetration has been developed. The prediction performance and accuracy of the CFD model was validated based on comparisons between its results and previous experimental data, and a good agreement was obtained. To evaluate the insulation performance of polyurethane foam with three different insulation thicknesses, the pressure changes and thermo-fluid characteristics in a partially liquid hydrogen tank, subject to fixed ambient temperature and wind velocity, were investigated numerically. It was confirmed that the numerical simulation results well describe not only the temporal variations in the thermal gradient due to coupling between the buoyance and convection, but also the buoyancy-driven turbulent flow characteristics inside liquid hydrogen storage tanks with different insulation thicknesses. In the future, the numerical model developed in this study will be used for optimizing the insulation systems of storage tanks for small-scale hydrogen liquefiers, which is a cost-effective and highly efficient approach.

Abstract Background Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. Methods We generated inducible satellite cell‐specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 CreERT2. To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin‐induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5‐ethynyl‐2'‐deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. Results Satellite cell‐specific Cdon ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon‐depleted myofibers exhibited 32 ± 9.6% of EdU‐positive satellite cells compared with 58 ± 4.4% satellite cells in control myofibers (P < 0.05). About 32.5 ± 3.7% Cdon‐ablated myoblasts were positive for senescence‐associated β‐galactosidase (SA‐β‐gal) while only 3.6 ± 0.5% of control satellite cells were positive (P < 0.001). Transcriptome analysis of muscles at post‐injury Day 4 revealed alterations in genes related to mitogen‐activated protein kinase signalling (P < 8.29 e−5) and extracellular matrix (P < 2.65 e−24). Consistent with this, Cdon‐depleted tibialis anterior muscles had reduced phosphorylated extracellular signal‐regulated kinase (p‐ERK) protein levels and expression of ERK targets, such as Fos (0.23‐fold) and Egr1 (0.31‐fold), relative to mock‐treated control muscles (P < 0.001). Cdon‐depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and/or mislocalized integrin β1 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 ± 1.9%, mock = 21.5 ± 6%, P < 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of FGFR1 and FGFR4, likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model, Zmpste24−/− myofibers, showed decreased Cdon levels (Cdon‐positive cells in Zmpste24−/− = 63.3 ± 11%, wild type = 90 ± 7.7%, P < 0.05) and integrin β1 activation (weak or mislocalized integrin β1 in Zmpste24−/− = 64 ± 6.9%, wild type = 17.4 ± 5.9%, P < 0.01). Conclusions Cdon deficiency in satellite cells causes impaired proliferation of satellite cells and muscle regeneration via aberrant integrin and FGFR signalling.

Background: As a process of aging, skeletal muscle mass and function gradually decrease. It is reported that ginsenoside Rb1 and Rb2 play a role as AMP-activated protein kinase activator, resulting in regulating glucose homeostasis, and Rb1 reduces oxidative stress in aged skeletal muscles through activating the phosphatidylinositol 3-kinase/Akt/Nrf2 pathway. We examined the effects of Rb1 and Rb2 on differentiation of the muscle stem cells and myotube formation. Methods: C2C12 myoblasts treated with Rb1 and/or Rb2 were differentiated and induced to myotube formation, followed by immunoblotting for myogenic marker proteins, such as myosin heavy chain, MyoD, and myogenin, or immunostaining for myosin heavy chain or immunoprecipitation analysis for heterodimerization of MyoD/E-proteins. Results: Rb1 and Rb2 enhanced myoblast differentiation through accelerating MyoD/E-protein heterodimerization and increased myotube hypertrophy, accompanied by activation of Akt/mammalian target of rapamycin signaling. In addition, Rb1 and Rb2 induced the MyoD-mediated transdifferentiation of the rhabdomyosarcoma cells into myoblasts. Furthermore, co-treatment with Rb1 and Rb2 had synergistically enhanced myoblast differentiation through Akt activation. Conclusion: Rb1 and Rb2 upregulate myotube growth and myogenic differentiation through activating Akt/mammalian target of rapamycin signaling and inducing myogenic conversion of fibroblasts. Thus, our first finding indicates that Rb1 and Rb2 have strong potential as a helpful remedy to prevent and treat muscle atrophy, such as age-related muscular dystrophy. Keywords: Akt/mTOR signaling, Hypertrophy, Myoblast differentiation, Rb1, Rb2

In the study here, the potential applicability of KMRC011 - an agonist of toll-like receptor-5 – as a countermeasure for radiation toxicities was evaluated. Following a single 5.5 Gy total body irradiation (TBI, surface absorbed dose = 7 Gy) of Co60 γ-rays, mortality rates and degrees of pathological lesions that developed over 80 days were compared in monkeys that received TBI only and a group that was injected once with KMRC011 (10 μg/kg) after TBI. Compared to the TBI-only hosts (80%), the death rate was significantly improved by the use of KMRC011 (40%), all deaths in both groups occurred in the period from Days 19-24 post-TBI. Further analysis of monkeys that survived until the end of the experiment showed that AST and ALT levels were elevated only in the TBI group, and that radiation-induced tissue damage was alleviated by the KMRC011 injection. Additionally, expression of cell death-related proteins was lower in tissues from the KMRC011-treated hosts than in those in the TBI-only group. Other measured parameters, including body weight, food uptake, and hematological values did not significantly differ between the two groups over the entire period. The results of this study, thus demonstrate that KMRC011 could potentially be used as a medical countermeasure for the treatment of acute radiation exposure.

Black chokeberry or aronia (the fruit of Aronia melanocarpa) has been reported to having pharmacological activities against metabolic syndrome, such as hypertension, obesity, diabetes, and pro-inflammatory conditions. However, the effects of aronia on myogenic differentiation and muscle homoeostasis are uncharacterized. In this study, we investigated the effects of aronia (black chokeberry) on myogenic differentiation and muscle metabolic functions in young mice. Aronia extract (AR) promotes myogenic differentiation and elevates the formation of multinucleated myotubes through Akt activation. AR protects dexamethasone (DEX)-induced myotube atrophy through inhibition of muscle-specific ubiquitin ligases mediated by Akt activation. The treatment with AR increases muscle mass and strength in mice without cardiac hypertrophy. AR treatment enhances both oxidative and glycolytic myofibers and muscle metabolism with elevated mitochondrial genes and glucose metabolism-related genes. Furthermore, AR-fed muscle fibers display increased levels of total OxPHOS and myoglobin proteins. Taken together, AR enhances myogenic differentiation and improves muscle mass and function, suggesting that AR has a promising potential as a nutraceutical remedy to intervene in muscle weakness and atrophy.

Growing evidence suggests that there is an essential link between the gut and lungs. Asthma is a common chronic inflammatory disease and is considered a heterogeneous disease. While it has been documented that eosinophilic asthma affects gut immunity and the microbiome, the effect of other types of asthma on the gut environment has not been examined. In this study, we utilized an OVA/poly I:C-induced mixed granulocytic asthma model and found increased Tregs without significant changes in other inflammatory cells in the colon. Interestingly, an altered gut microbiome has been observed in a mixed granulocytic asthma model. We observed an increase in the relative abundance of the Faecalibaculum genus and Erysipelotrichaceae family, with a concomitant decrease in the relative abundance of the genera Candidatus arthromitus and Streptococcus. The altered gut microbiome leads to changes in the abundance of genes associated with microbial metabolism, such as glycolysis. We found that mixed granulocytic asthma mainly affects the gut microbial composition and metabolism, which may have important implications in the severity and development of asthma and gut immune homeostasis. This suggests that altered gut microbial metabolism may be a potential therapeutic target for patients with mixed granulocytic asthma.

Arginine methylation mediated by protein arginine methyltransferases (PRMTs) is a post-translational modification of both histone and non-histone substrates related to diverse biological processes. PRMTs appear to be critical regulators in skeletal muscle physiology, including regeneration, metabolic homeostasis, and plasticity. Chronic inflammation is commonly associated with the decline of skeletal muscle mass and strength related to aging or chronic diseases, defined as sarcopenia. In turn, declined skeletal muscle mass and strength can exacerbate chronic inflammation. Thus, understanding the molecular regulatory pathway underlying the crosstalk between skeletal muscle function and inflammation might be essential for the intervention of muscle pathophysiology. In this review, we will address the current knowledge on the role of PRMTs in skeletal muscle physiology and pathophysiology with a specific emphasis on its relationship with inflammation.

Background: The ginsenoside Rg1 has been shown to exert various pharmacological activities with health benefits. Previously, we have reported that Rg1 promoted myogenic differentiation and myotube growth in C2C12 myoblasts. In this study, the in vivo effect of Rg1 on fiber-type composition and oxidative metabolism in skeletal muscle was examined. Methods: To examine the effect of Rg1 on skeletal muscle, 3-month-old mice were treated with Rg1 for 5 weeks. To assess muscle strength, grip strength tests were performed, and the lower hind limb muscles were harvested, followed by various detailed analysis, such as histological staining, immunoblotting, immunostaining, and real-time quantitative reverse transcription polymerase chain reaction. In addition, to verify the in vivo data, primary myoblasts isolated from mice were treated with Rg1, and the Rg1 effect on myotube growth was examined by immunoblotting and immunostaining analysis. Results: Rg1 treatment increased the expression of myosin heavy chain isoforms characteristic for both oxidative and glycolytic muscle fibers; increased myofiber sizes were accompanied by enhanced muscle strength. Rg1 treatment also enhanced oxidative muscle metabolism with elevated oxidative phosphorylation proteins. Furthermore, Rg1-treated muscles exhibited increased levels of anabolic S6 kinase signaling. Conclusion: Rg1 improves muscle functionality via enhancing muscle gene expression and oxidative muscle metabolism in mice. Keywords: Atrophy, Exercise-specific signaling, Ginsenoside, Rg1, Skeletal muscle

The authors wish to make the following corrections to this paper [...]

Acquisition of acquired chemoresistance during treatment cycles in urothelial carcinoma of the bladder (UCB) is the major cause of death through enhancing the risk of cancer progression and metastasis. Elevated glucose flux through the abnormal upregulation of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) controls key signaling and metabolic pathways regulating diverse cancer cell phenotypes. This study showed that OGT expression levels in two human UCB cell models with acquired resistance to gemcitabine and paclitaxel were significantly upregulated compared with those in parental cells. Reducing hyper-O-GlcNAcylation by OGT knockdown (KD) markedly facilitated chemosensitivity to the corresponding chemotherapeutics in both cells, and combination treatment with OGT-KD showed more severe growth defects in chemoresistant sublines. We subsequently verified the suppressive effects of OGT-KD monotherapy on cell migration/invasion in vitro and xenograft tumor growth in vivo in chemoresistant UCB cells. Transcriptome analysis of these cells revealed 97 upregulated genes, which were enriched in multiple oncogenic pathways. Our final choice of suspected OGT glycosylation substrate was VCAN, S1PR3, PDGFRB, and PRKCG, the knockdown of which induced cell growth defects. These findings demonstrate the vital role of dysregulated OGT activity and hyper-O-GlcNAcylation in modulating treatment failure and tumor aggression in chemoresistant UCB.

INTRODUCTION:Chimeric antigen receptor (CAR) T-cells have been recently developed and are producing impressive outcomes in patients with hematologic malignancies. However, there is no standardized method for cell trafficking and in vivo CAR T-cell monitoring. We assessed the feasibility of real-time in vivo 89Zr-p-Isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS, DFO) labeled CAR T-cell trafficking using positron emission tomography (PET). RESULTS:The 89Zr-DFO radiolabeling efficiency of Jurkat/CAR and human peripheral blood mononuclear cells (hPBMC)/CAR T-cells was 70%-79%, and cell radiolabeling activity was 98.1-103.6 kBq/106 cells. Cell viability after radiolabeling was >95%. Cell proliferation was not significantly different during the early period after radiolabeling, compared with unlabeled cells; however, the proliferative capacity decreased over time (day 7 after labeling). IL-2 or IFN-γ secretion was not significantly different between unlabeled and labeled CAR T-cells. PET/magnetic resonance imaging in the xenograft model showed that most of the 89Zr-DFO-labeled Jurkat/CAR T-cells were distributed in the lung (24.4% ± 3.4%ID) and liver (22.9% ± 5.6%ID) by one hour after injection. The cells gradually migrated from the lung to the liver and spleen by day 1, and remained stable in these sites until day 7 (on day 7: lung 3.9% ± 0.3%ID, liver 36.4% ± 2.7%ID, spleen 1.4% ± 0.3%ID). No significant accumulation of labeled cells was identified in tumors. A similar pattern was observed in ex vivo biodistributions on day 7 (lung 3.0% ± 1.0%ID, liver 19.8% ± 2.2%ID, spleen 2.3% ± 1.7%ID). 89Zr-DFO-labeled hPBMC/CAR T-cells showed a similar distribution, compared with Jurkat/CAR T-cells, on serial PET images. CAR T cell distribution was cross-confirmed by flow cytometry, Alu polymerase chain reaction, and immunohistochemistry. CONCLUSION:Real-time in vivo cell trafficking is feasible using PET imaging of 89Zr-DFO-labeled CAR T-cells. This can be used to investigate cellular kinetics, initial in vivo biodistribution, and safety profiles in future CAR T-cell development.

Neuromuscular diseases (NMDs) are characterized by progressive loss of muscle mass and strength that leads to impaired body movement. It not only severely diminishes the quality of life of the patients, but also subjects them to increased risk of secondary medical conditions such as fall-induced injuries and various chronic diseases. However, no effective treatment is currently available to prevent or reverse the disease progression. Protein arginine methyltransferases (PRMTs) are emerging as a potential therapeutic target for diverse diseases, such as cancer and cardiovascular diseases. Their expression levels are altered in the patients and molecular mechanisms underlying the association between PRMTs and the diseases are being investigated. PRMTs have been shown to regulate development, homeostasis, and regeneration of both muscle and neurons, and their association to NMDs are emerging as well. Through inhibition of PRMT activities, a few studies have reported suppression of cytotoxic phenotypes observed in NMDs. Here, we review our current understanding of PRMTs’ involvement in the pathophysiology of NMDs and potential therapeutic strategies targeting PRMTs to address the unmet medical need.

Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing heterodimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

In a previous report, 3-aminopropyl functionalized magnesium phyllosilicate (aminoclay) improved adenovirus transduction efficiency by shielding the negative surface charges of adenovirus particles. The present study analyzed the physicochemical characterization of the electrostatic complex of adenoviruses with aminoclay and explored whether it could be utilized for enhancing tumor suppressive activity in the bladder. As a result of aminoclay-adenovirus nanobiohybridization, its transduction was enhanced in a dose-dependent manner, increasing transgene expression in bladder cancer cells and in in vivo animal models. Physicochemical studies demonstrated that positively charged aminoclay led to the neutralization of negative surface charges of adenoviruses, protection of adenoviruses from neutralizing antibodies and lowered transepithelial electrical resistance (TEER). As expected from the physicochemical properties, the aminoclay enabled tumor-targeting adenoviruses to be more potent in killing bladder cancer cells and suppressing tumor growth in orthotopic bladder tumors, suggesting that aminoclay would be an efficient, versatile and biocompatible delivery carrier for intravesical instillation of adenoviruses.

FLASH radiotherapy is an emerging radiotherapy technique used to spare normal tissues. It employs ultra-high dose rate radiation beams over 40 Gy/s, which is significantly higher than those of conventional radiotherapy. In this study, a fiber-optic radiation sensor (FORS) was fabricated using a plastic scintillator, an optical filter, and a plastic optical fiber to measure the ultra-high dose rate electron beams over 40 Gy/s used in FLASH radiotherapy. The radiation-induced emissions, such as Cherenkov radiation and fluorescence generated in a transmitting optical fiber, were spectrally discriminated from the light outputs of the FORS. To evaluate the linearity and dose rate dependence of the FORS, the outputs of the fiber-optic radiation sensor were measured according to distances from an electron scattering device, and the results were compared with those of an ionization chamber and radiochromic films. Finally, the percentage depth doses were obtained using the FORS as a function of depth in a water phantom. This study found that ultra-high dose rate electron beams over 40 Gy/s could be measured in real time using a FORS.

Preservation of muscle stem cell function is critical for muscle homeostasis and the regenerative capacity of stem cells declines with age, leading to muscle loss. Previously, daidzein, a natural isoflavone from Leguminosae, has been shown to prevent TNF-α-induced muscle atrophy. However, the molecular mechanisms of daidzein in these processes are currently unknown. In this study, we demonstrate a positive effect of black soybean extract (BS Ext) and daidzein on myoblast differentiation and myotube growth. Daidzein prevents dexamethasone-induced myotube atrophy through Akt activation. The promyogenic effect of BS Ext and daidzein is mediated through two promyogenic kinases, Akt and p38MAPK that in turn activates a key myogenic transcription factor MyoD. Additionally, BS Ext and daidzein promote myotube growth through Akt/mTOR/S6K pathway. Finally, daidzein augments MyoD-dependent myogenic conversion of mouse embryonic fibroblasts. Taken together, our data suggest that daidzein promotes myogenic differentiation and myotube hypertrophy through p38 and Akt/mTOR/S6K pathway.

Background: Ginsenoside Rg1 belongs to protopanaxatriol-type ginsenosides and has diverse pharmacological activities. In this report, we investigated whether Rg1 could upregulate muscular stem cell differentiation and muscle growth. Methods: C2C12 myoblasts, MyoD-transfected 10T1/2 embryonic fibroblasts, and HEK293T cells were treated with Rg1 and differentiated for 2 d, subjected to immunoblotting, immunocytochemistry, or immunoprecipitation. Results: Rg1 activated promyogenic kinases, p38MAPK (mitogen-activated protein kinase) and Akt signaling, that in turn promote the heterodimerization with MyoD and E proteins, resulting in enhancing myogenic differentiation. Through the activation of Akt/mammalian target of rapamycin pathway, Rg1 induced myotube growth and prevented dexamethasone-induced myotube atrophy. Furthermore, Rg1 increased MyoD-dependent myogenic conversion of fibroblast. Conclusion: Rg1 upregulates promyogenic kinases, especially Akt, resulting in improvement of myoblast differentiation and myotube growth.

Abstract Carbon nanotube/polytetrafluoroethylene composite polymer targets are proposed for use in the fabrication of fluorocarbon thin films using the mid-frequency sputtering process. Fluorocarbon thin films deposited using carbon nanotube/polytetrafluoroethylene composite targets exhibit an amorphous phase with a smooth surface and show a high water contact angle, optical transmittance, and surface hardness. X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy studies reveal that as the carbon nanotube concentration increased in the composite target, a carbon cross-linked structure was formed, which enhanced the film hardness and the modulus of the fluorocarbon thin film. Large-area fluorocarbon thin films with a substrate width of 700 mm were successfully fabricated by a pilot-scale roll-to-roll sputtering system using a carbon nanotube/polytetrafluoroethylene composite target.

Studies have shown that insertion of oleic acid into lipid bilayers can modulate the membrane properties of liposomes so as to improve their function as drug carriers. Considering that 2-hydroxyoleic acid (2OHOA), a potential antitumor agent currently undergoing clinical trials, is a derivative of oleic acid, we explored the possibility of developing 2OHOA-inserted liposomes as a multifunctional carrier of antitumor drugs in the present study. The insertion of 2OHOA into lipid bilayers was confirmed by surface charge determination and differential scanning calorimetry. 2OHOA insertion greatly decreased the order of dimyristoylphosphatidylcholine packing, produced a nanosized (

Microbiota plays a critical role in the overall growth performance and health status of dairy cows, especially during their early life. Several studies have reported that fecal microbiome of neonatal calves is shifted by various factors such as diarrhea, antibiotic treatment, or environmental changes. Despite the importance of gut microbiome, a lack of knowledge regarding the composition and functions of microbiota impedes the development of new strategies for improving growth performance and disease resistance during the neonatal calf period. In this study, we utilized next-generation sequencing to monitor the time-dependent dynamics of the gut microbiota of dairy calves before weaning (1–8 weeks of age) and further investigated the microbiome changes caused by diarrhea. Metagenomic analysis revealed that continuous changes, including increasing gut microbiome diversity, occurred from 1 to 5 weeks of age. However, the composition and diversity of the fecal microbiome did not change after 6 weeks of age. The most prominent changes in the fecal microbiome composition caused by aging at family level were a decreased abundance of Bacteroidaceae and Enterobacteriaceae and an increased abundance of Prevotellaceae. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis indicated that the abundance of microbial genes associated with various metabolic pathways changed with aging. All calves with diarrhea symptoms showed drastic microbiome changes and about a week later returned to the microbiome of pre-diarrheal stage regardless of age. At phylum level, abundance of Bacteroidetes was decreased (p = 0.09) and that of Proteobacteria increased (p = 0.07) during diarrhea. PICRUSt analysis indicated that microbial metabolism-related genes, such as starch and sucrose metabolism, sphingolipid metabolism, alanine aspartate, and glutamate metabolism were significantly altered in diarrheal calves. Together, these results highlight the important implications of gut microbiota in gut metabolism and health status of neonatal dairy calves.

Study DesignDescriptions of technical strategies to overcome pitfalls associated with early learning periods in biportal endoscopic spinal surgery (BESS).PurposeTo introduce BESS for lumbar spinal diseases (LSDs) and to inform certain challenges to be overcome in mastering the technique.Overview of LiteratureBESS has shown superior benefits including excellent magnification, a wider range of view by dynamic handling of an endoscope and instruments. Clinical reports, however, have not yet been very revealing for its new introduction into minimally invasive spine surgery.MethodsTo evaluate the learning curve for BESS, the procedures for various LSDs by one surgeon were analyzed in the view of shortening of the operating times and reduction of complications. Reviewing of recorded procedures helped in finding the reasons and the implemented solutions.ResultsThe 68 cases included 25 for lumbar disc herniation (LDH), 3 for revision for recurred LDH, 39 for lumbar spinal stenosis (LSS) and 1 for synovial cyst. The operation time for the total cases averaged 83.7±33.6 minutes. According to diagnosis, it was 68.2±23.7 minutes for LDH. After the 14th case of LDH, it was nearly constant and close to the average time. One level of LSS needed 110.4±34.4 minutes. Prolonged operation times even in some later cases of LSS were mainly from struggling against blurred vision due to epidural bleeding. There were 7 cases of complications (10.3%) including 2 cases of dural tear, 1 case of root injury, and 4 cases of incomplete decompression on postoperative magnetic resonance imaging. There was no case of symptomatic hematoma or wound infection.ConclusionsBESS seemed to have a relatively short learning curve period. The overall complication rate in early learning period was 10.3%. These could be avoided by magnified regional views on an endoscope and a clear surgical field by controlling epidural bleeding.

For oropharyngeal squamous cell carcinoma (OPSCC), there are not enough additional robust biomarkers for subgrouping after the distinct classification using p16. As SOX2 is an emerging biomarker for cancer treatment, its clinical implication in OPSCC was evaluated using a consecutive tissue microarray (TMA) cohort consisting of 111 patients who underwent surgery as an initial treatment from May 2002 to December 2016 and 79 patients in The Cancer Genome Atlas (TCGA) dataset. In both datasets, p16+/SOX2High (HPV+/SOX2High in TCGA) showed the best prognosis among the four groups classified by SOX2 and p16 for 5-year overall survival (OS) and recurrence (all p < 0.05), but SOX2 did not make a significant difference in the prognosis of the p16− group. In the TMA cohort, SOX2High was significantly correlated with response to radiotherapy and lower pathologic T classification in the p16+ group (p = 0.001). In TCGA, correlations between SOX2 and tumor stage classification or radiotherapy were not observed; however, HPV+/SOX2High had a significantly low tumor mutation burden among the four groups (all p < 0.05). In summary, SOX2 was proven to be a potential marker to predict overall survival and recurrence in p16+ OPSCC. However, the role of SOX2 has not yet been confirmed in p16− OPSCC patients.

This paper presents a CMOS depth image sensor with offset pixel aperture (OPA) using a back-side illumination structure to improve disparity. The OPA method is an efficient way to obtain depth information with a single image sensor without additional external factors. Two types of apertures (i.e., left-OPA (LOPA) and right-OPA (ROPA)) are applied to pixels. The depth information is obtained from the disparity caused by the phase difference between the LOPA and ROPA images. In a CMOS depth image sensor with OPA, disparity is important information. Improving disparity is an easy way of improving the performance of the CMOS depth image sensor with OPA. Disparity is affected by pixel height. Therefore, this paper compared two CMOS depth image sensors with OPA using front-side illumination (FSI) and back-side illumination (BSI) structures. As FSI and BSI chips are fabricated via different processes, two similar chips were used for measurement by calculating the ratio of the OPA offset to pixel size. Both chips were evaluated for chief ray angle (CRA) and disparity in the same measurement environment. Experimental results were then compared and analyzed for the two CMOS depth image sensors with OPA.

Herein, an antireflection and superhydrophobic film was obtained by uniformly forming nanostructures on the surface of polyethylene terephthalate (PET) substrate using oxygen plasma without a pattern mask and coating plasma-polymer-fluorocarbon (PPFC) on the nanostructured surface by mid-range frequency sputtering. PPFC/nanostructured-PET showed a reflectance of 4.2%, which is 56% lower than that of the PET film. Haze was also improved. Nanostructured-PET exhibited a superhydrophilic surface due to plasma deformation and a superhydrophobic surface could be realized by coating PPFC on the nanostructured surface. The PPFC coating prevented the aging of polymer film nanostructures and showed excellent durability in a high-temperature and high-humidity environment. It exhibited excellent flexibility to maintain the superhydrophobic surface, even at a mechanical bending radius of 1 mm, and could retain its properties even after repeated bending for 10,000 times.

Mycobacterium abscessus is a prominent cause of pulmonary infection in immunosuppressed patients and those with cystic fibrosis. Nucleotide-binding oligomerization domain (NOD) 2 is a cytosolic receptor which senses a bacterial peptidoglycan component, muramyl dipeptide (MDP). Although nucleotide-binding oligomerization domain 2 (NOD2) contributes to protect host against various microbial infections, it is still unclear whether NOD2 is essential to regulate host immune responses against M. abscessus infection. In this study, we sought to clarify the role of NOD2 and the underlying mechanism in host defense against M. abscessus infection. Mice were infected intranasally with M. abscessus and sacrificed at indicated time points. Bacterial survival, cytokines production, and pathology in the lungs were determined. Bone marrow-derived macrophages were used to clarify cellular mechanism of NOD2-mediated immune response. Bacterial clearance was impaired, and pathology was more severe in the lungs of NOD2-deficient mice compared with the wild-type mice. In macrophages, NOD2-mediated activation of p38 and JNK were required for production of proinflammatory cytokines and nitric oxide (NO) and expression of iNOS in response to M. abscessus. NO was critical for limiting intracellular growth of the pathogen. Intranasal administration of MDP reduced in vivo bacterial replication and thus improved lung pathology in M. abscessus-infected mice. This study offers important new insights into the potential roles of the NOD2 in initiating and potentiating innate immune response against M. abscessus pulmonary infection.

Prevention of age-associated reduction in muscle mass and function is required to manage a healthy life. Supplemental (-)-Epicatechin (EC) appears to act as a potential regulator for muscle growth and strength. However, its cellular and molecular mechanisms as a potential muscle growth agent have not been studied well. In the current study, we investigated a role of EC in differentiation of muscle progenitors to gain the molecular insight into how EC regulates muscle growth. EC enhanced myogenic differentiation in a dose-dependent manner through stimulation of promyogenic signaling pathways, p38MAPK and Akt. EC treatment elevated MyoD activity by enhancing its heterodimerization with E protein. Consistently, EC also positively regulated myogenic conversion and differentiation of fibroblasts. In conclusion, EC has a potential as a therapeutic or nutraceutical remedy to treat degenerative muscle diseases or age-related muscle weakness.

Sonic hedgehog (Shh) signaling is required for numerous developmental processes including specification of ventral cell types in the central nervous system such as midbrain dopaminergic (DA) neurons. The multifunctional coreceptor Cdo increases the signaling activity of Shh which is crucial for development of forebrain and neural tube. In this study, we investigated the role of Cdo in midbrain DA neurogenesis. Cdo and Shh signaling components are induced during neurogenesis of embryonic stem (ES) cells. Cdo−/− ES cells show reduced neuronal differentiation accompanied by increased cell death upon neuronal induction. In addition, Cdo−/− ES cells form fewer tyrosine hydroxylase (TH) and microtubule associated protein 2 (MAP2)-positive DA neurons correlating with the decreased expression of key regulators of DA neurogenesis, such as Shh, Neurogenin2, Mash1, Foxa2, Lmx1a, Nurr1 and Pitx3, relative to the Cdo+/+ ES cells. Consistently, the Cdo−/− embryonic midbrain displays a reduction in expression of TH and Nurr1. Furthermore, activation of Shh signaling by treatment with Purmorphamine (Pur) restores the DA neurogenesis of Cdo−/− ES cells, suggesting that Cdo is required for the full Shh signaling activation to induce efficient DA neurogenesis.

This study was conducted in order to investigate whether the presence of light or different colors of light would influence the energy expenditure and behavior of broiler chickens. Eight 8-week-old broiler chickens were adapted to a respiration chamber (Length, 28.5 cm; Height, 38.5 cm; Width, 44.0 cm) for one week prior to the initiation of the experiment. In experiment 1, energy expenditure and behavior of the chickens were analyzed in the presence or absence of light for four days. Chickens were exposed to 6 cycles of 2 h light/2 h dark period per day. In experiment 2, the broiler chickens that had been used in experiment 1 were used to evaluate the effect of 4 different wavelength light-emitting diodes (LEDs) on the energy expenditure and behavior of broiler chickens. The LEDs used in this study had the following wavelength bands; white (control), red (618 to 635 nm), green (515 to 530 nm) and blue (450 to 470 nm). The chickens were randomly exposed to a 2-h LED light in a random and sequential order per day for 3 days. Oxygen consumption and carbon dioxide production of the chickens were recorded using an open-circuit calorimeter system, and energy expenditure was calculated based on the collected data. The behavior of the chickens was analyzed based on following categories i.e., resting, standing, and pecking, and closed-circuit television was used to record these behavioral postures. The analysis of data from experiment 1 showed that the energy expenditure was higher (p

This paper presents the effects of offset pixel aperture width on the performance of monochrome (MONO) CMOS image sensors (CISs) for a three-dimensional image sensor. Using a technique to integrate the offset pixel aperture (OPA) inside each pixel, the depth information can be acquired using a disparity from OPA patterns. The OPA is classified into two pattern types: Left-offset pixel aperture (LOPA) and right-offset pixel aperture (ROPA). These OPAs are divided into odd and even rows and integrated in a pixel array. To analyze the correlation between the OPA width and the sensor characteristics, experiments were conducted by configuring the test elements group (TEG) regions. The OPA width of the TEG region for the measurement varied in the range of 0.3–0.5 μm. As the aperture width decreased, the disparity of the image increased, while the sensitivity decreased. It is possible to acquire depth information by the disparity obtained from the proposed MONO CIS using the OPA technique without an external light source. Therefore, the proposed MONO CIS with OPA could easily be applied to miniaturized devices. The proposed MONO CIS was designed and manufactured using the 0.11 μm CIS process.

We propose a new method of fabricating metal–polymer composite targets for sputtering, which makes it easier to control the composition and enables the homogeneous and reproducible fabrication of metal–polymer nanocomposites over large areas. Using Cu/polytetrafluoroethylene composite targets containing 20, 50, and 80 wt.% Cu, Cu/plasma polymer fluorocarbon (PPFC) nanocomposite thin films were prepared by radio-frequency (RF) sputtering. Targets with 80 wt.% Cu were conductive; moreover, sputtering was possible not only with RF but also with mid-range frequency (MF) and direct current (DC) power sources. The nanocomposite thin film deposited by MF and DC power using an 80 wt.% Cu target showed near-metallic characteristics, exhibited absorption peaks at 618 and 678 nm, and had a surface resistance of 2 × 104 and 34.55 Ω/sq, respectively. We also analyzed the structure and composition of the Cu/PPFC nanocomposite films by X-ray diffraction and X-ray photoelectron spectroscopy. The described metal–polymer targets can advance the applications and commercialization of nanocomposite thin films.

A complementary metal oxide semiconductor (CMOS) image sensor (CIS), using offset pixel aperture (OPA) technique, was designed and fabricated using the 0.11-µm CIS process. In conventional cameras, an aperture is located on the camera lens. However, in a CIS camera using OPA technique, apertures are integrated as left-offset pixel apertures (LOPAs) and right-offset pixel apertures (ROPAs). A color pattern is built, comprising LOPA, blue, red, green, and ROPA pixels. The disparity information can be acquired from the LOPA and ROPA channels. Both disparity information and two-dimensional (2D) color information can be simultaneously acquired from the LOPA, blue, red, green, and ROPA channels. A geometric model of the OPA technique is constructed to estimate the disparity of the image, and the measurement results are compared with the estimated results. Depth extraction is thus achieved by a single CIS using the OPA technique, which can be easily adapted to commercial CIS cameras.

This paper presents a low power and high speed 3D-DWT (three-dimensional discrete wavelet transform) architecture using stacked silicon dies for image compression of medical images. The interconnections of stacked chips are based on TSV (through silicon via) techniques. Its low power operation is due to short signal paths between layers. The area of 3D architecture is much smaller than that of 2D counterpart having the same performance. Each circuit/system layer can be optimized since it can be fabricated using a different technology. The 3D-DWT architecture consists of two processing elements (PE): a PE-odd (processing elements-odd) and a PE-even (processing elements-even) layer. Each layer processes pixel data derived from rows of the y axis, scanning from left to right side of the image data. Each layer operates in parallel yielding high throughput. The architecture can be used to compress medical image such as X-ray, MRI, NRI, CT and endoscopy by processing images frame by frame.

Relative dynamic models of satellites which describe the relative motion between two satellites is fundamental for research on the formation flying. The accuracy of various linearized or nonlinear models of relative motion is analyzed and compared. A `Modeling Error Index (MEI)` is defined for evaluating the accuracy of models. The accuracy of the relative dynamic models in various orbit circumstance are obtained by calculating the modeling error with various eccentricities of the chief orbit and distances between the chief and the deputy. It is found that the modeling errors of the relative dynamic models have different values according to the eccentricity, J2 perturbation, and the distance between satellites. Since the evaluated accuracy of various models in this paper means the error of dynamic models of the formation flying, the results of this paper are very useful for choosing the appropriate relative model of the formation flying mission.

ObjectiveThe sound of running water (SRW) has been effectively used for toilet training during toddlerhood. However, the effect of SRW on voiding functions in adult males with lower urinary tract symptoms (LUTS) has not been evaluated. To determine the effect of SRW on urination in male patients with LUTS, multiple voiding parameters of uroflowmetry with postvoid residual urine (PVR) were assessed according to the presence of SRW played by a mobile application.MethodsEighteen consecutive male patients with LUTS were prospectively enrolled between March and April 2014. Uroflowmetry with PVR measured by a bladder scan was randomly performed once weekly for two consecutive weeks with and without SRW in a completely sealed room after pre-checked bladder volume was scanned to be more than 150 cc. SRW was played with river water sounds amongst relaxed melodies from a smartphone mobile application.ResultsThe mean age of enrolled patients and their mean International Prostate Symptom Score (IPSS) were 58.9 ± 7.7 years (range: 46-70) and 13.1 ± 5.9, respectively. All patients had not been prescribed any medications, including alpha-blockers or anti-muscarinic agents, in the last 3 months. There was a significant increase in mean peak flow rate (PFR) with SRW in comparison to without SRW (15.7 mL/s vs. 12.3 mL/s, respectively, p = 0.0125). However, there were no differences in other uroflowmetric parameters, including PVR.ConclusionsThe study showed that SRW from a mobile phone application may be helpful in facilitating voiding functions by increasing PFR in male LUTS patients.

Current treatments for tendon injuries often fail to fully restore joint biomechanics leading to the recurrence of symptoms, and thus resulting in a significant health problem with a relevant social impact worldwide. Cell-based approaches involving the use of stem cells might enable tailoring a successful tendon regeneration outcome. As growth factors (GFs) powerfully regulate the cell biological response, their exogenous addition can further stimulate stem cells into the tenogenic lineage, which might eventually depend on stem cells source. In the present study we investigate the tenogenic differentiation potential of human- amniotic fluid stem cells (hAFSCs) and adipose-derived stem cells (hASCs) with several GFs associated to tendon development and healing; namely, EGF, bFGF, PDGF-BB and TGF-β1. Stem cells response to biochemical stimuli was studied by screening of tendon-related genes (collagen type I, III, decorin, tenascin C and scleraxis) and proteins found in tendon extracellular matrix (ECM) (Collagen I, III, and Tenascin C). Despite the fact that GFs did not seem to influence the synthesis of tendon ECM proteins, EGF and bFGF influenced the expression of tendon-related genes in hAFSCs, while EGF and PDGF-BB stimulated the genetic expression in hASCs. Overall results on cellular alignment morphology, immunolocalization and PCR analysis indicated that both stem cell source can be biochemically induced towards tenogenic commitment, validating the potential of hASCs and hAFSCs for tendon regeneration strategies.