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Background COVID-19 patients requiring mechanical ventilation may develop significant pneumomediastinum and sub-cutaneous emphysema without associated pneumothorax (SWAP). Prophylactic chest tube placement or sub-fascial "blowholes" are usually recommended to prevent tension pneumothorax and clinical decline. Risk of iatrogenic lung injury and release of virus into the environment is high. Incidence and conservative management data of such barotraumatic complications during the COVID-19 pandemic are lacking. Methods All patients with mediastinal air and SWAP evaluated by the department of Thoracic Surgery at the Mount Sinai Hospital between March 30 and April 10, 2020 were identified. All patients without pneumothorax were treated conservatively with daily chest x-ray and observation. Three patients had prophylactic chest tube placement prior to the study period without thoracic surgery consultation. Results There were 29 cases of mediastinal air with SWAP out of 171 COVID positive intubated patients (17.0%) who were treated conservatively. Patients were intubated for an average of 2.4 days before SWAP was identified. 12 patients (41%) had improvement or resolution without intervention. Two patients progressed to pneumothorax 3 and 8 days following initial presentation. Both had chest tubes placed without incident before there were any changes in oxygenation, hemodynamics, supportive medications, or ventilator settings. There were 3 patients who had percutaneous tubes placed before the study period all of whom had significant worsening of their sub-cutaneous air and air leak. Conclusions Conservative management of massive sub-cutaneous emphysema without pneumothorax in COVID-19 patients is safe and limits viral exposure to healthcare workers. Placement of chest tubes is discouraged unless a definite sizable pneumothorax develops.

Mitochondria continuously fuse and divide to maintain homeostasis. An impairment in the balance between the fusion and fission processes can trigger mitochondrial dysfunction. Accumulating evidence suggests that mitochondrial dysfunction is related to neurodegenerative diseases such as Parkinson's disease (PD), with excessive mitochondrial fission in dopaminergic neurons being one of the pathological mechanisms of PD. Here, we investigated the balance between mitochondrial fusion and fission in the substantia nigra of a non-human primate model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. We found that MPTP induced shorter and abnormally distributed mitochondria. This phenomenon was accompanied by the activation of dynamin-related protein 1 (Drp1), a mitochondrial fission protein, through increased phosphorylation at S616. Thereafter, we assessed for activation of the components of the cyclin-dependent kinase 5 (CDK5) and extracellular signal-regulated kinase (ERK) signaling cascades, which are known regulators of Drp1(S616) phosphorylation. MPTP induced an increase in p25 and p35, which are required for CDK5 activation. Together, these findings suggest that the phosphorylation of Drp1(S616) by CDK5 is involved in mitochondrial fission in the substantia nigra of a non-human primate model of MPTP-induced PD., Graphical Abstract

Background/Aim: Staphylococcus aureus (S. aureus) is a major gram-positive pathogen, which can cause toxic and immunogenic injuries both in nosocomial and community-acquired infections. Peroxiredoxin (Prx) I plays crucial roles in cellular apoptosis, proliferation, and signal transduction as well as in immunoregulation. The present study aimed to investigate whether Prx I protects mice from death caused by the heat-killed Staphylococcus aureus. Materials and Methods: In the present study, we challenged the wild-type and Prx I-deficient mice with heat-killed S. aureus (HKSA). The effects of Prx I were evaluated by a series of in vitro and in vivo experiments including western blot, Haematoxylin and Eosin staining, splenocyte analysis and cytokines analysis. Results: Intra-peritoneal (ip) inoculation of HKSA resulted in increased mortality of Prx I-knockout (KO) mice with severe liver damage and highly populated spleens with lymphocytes. Furthermore, HKSA infections also bursted the production of both pro-inflammatory and anti-inflammatory serum cytokines in Prx I KO compared to wild-type mice. Conclusion: Enhanced mortality of S. aureus-infected mice with Prx I deficiency suggested that Prx I may protect against the infection-associated lethality of mice.

In cancer, activation of X-box binding protein (XBP1) has a critical role in tumorigenesis and cancer progression. Transcriptional regulatory mechanism of XBP1 in cancer development has been well known, however, regulation of ubiquitination and degradation of XBP1 has not been elucidated yet. Here we show that Fbw7, a substrate recognition component of the SKP1-Cullin-F-box-type E3 ligase, interacts with XBP1 in a phosphorylation-dependent manner, and facilitates XBP1 ubiquitination and protein degradation. Moreover, Fbw7 inhibits oncogenic pathways including NF-κB, AP1, and Myc induced by XBP1. Interestingly, XBP1 negatively regulates transcription of Fbw7 via a feedback mechanism through NF-κB/E2F-1 axis signaling pathway, suggesting that overexpression of XBP1s may contribute to low level of Fbw7 expression in human cancers. Therefore, a negative feedback loop between Fbw7 and XBP1 contributes to the regulation of tumor development and can be an attractive target for novel therapy in cancers.

Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono‑ and di‑methylated ninth lysine of histone 3 and belongs to the Jumonji domain‑containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor‑mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small‑sized eyes and abnormal pigmentation. Whole‑mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.

In this paper, an intra prediction method is proposed for coding of depth pictures using plane modelling. Each pixel in the depth picture is related to the distance from a camera to an object surface, and pixels corresponding to a flat surface of an object form a relationship with the 2D plane surface. The plane surface can be represented by a simple equation in the 3D camera coordinate system in such a way that the coordinate system of depth pixels can be transformed to the camera coordinate system. This paper finds the parameters which define the plane surface closest to given depth pixels. The plane model is then used to predict the depth pixels on the plane surface. A depth prediction method is also devised for efficient intra prediction of depth pictures, using variable-size blocks. For prediction with variable-size blocks, the plane surface that occupies a large part of the picture can be predicted using a large block size. The simulation results of the proposed method show that the mean squared error is reduced by up to 96.6% for a block size of 4 × 4 pixels and reduced by up to 98% for a block size of 16 × 16, compared with the intra prediction modes of H.264/AVC and H.265/HEVC.

Parkinson’s disease (PD) comprises an age-related and the second most common disorders which is characterized by progressive motor symptoms such as bradykinesia, rigidity, akinesia, abnormal posture, and resting tremor. The pathology of PD involves the loss of dopaminergic (DA) neurons from the substantia nigra and the production α-synuclein-containing Lewy bodies and Lewy neurites. Current pharmacological treatments for PD target early symptoms by supplying dopamine precursors. These treatments regrettably have long-term side-effects, whereas stem cells-based therapies demonstrate safety and efficiency in preclinical studies through enhancement of dopamine uptake and motor symptoms. Therefore, stem cell transplantation shows great promise as a method to replace lost DA neurons; and for acquiring a better understanding of these neurodegenerative diseases mechanisms. In this review, we discuss recent preclinical studies of stem cell-based therapy for PD and important areas of future research.

The tandem configuration consisting of two or more solar cells is practically the only approach to overcome the Shockley-Queisser limit, as evidenced by the III-V multijunction solar cells. From theoretical calculation, it has been found that the combination of a top cell with a large bandgap energy (e.g. 1.5~1.7 eV) and a bottom cell with a low bandgap energy (e.g. 1.0~1.1 eV) can lead to a conversion efficiency higher than 30%. Given that the bandgap energy of most commercial single junction solar cells is around 1.1 eV, the perovskite solar cells with a bandgap energy around 1.6 eV must be a very promising candidate for the top cell of tandem solar cells. In this presentation, I will discuss the essential requirements for preparing highly performing perovskite top cells of perovskite-based tandem solar cells. Firstly, the strategies for improving the performance of the p-i-n type planar perovskite solar cell, mostly focusing on the interfacial charge transfer, will be introduced. After a series of interfacial engineering procedures to the charge extraction layers, a conversion efficiency as high as 19% could be achieved. Secondly, strategies for fabricating transparent perovskite solar cells with a TCO top electrode layer will be discussed. Finally, some of the recent results on the highly efficient (> 23%) tandem solar cells incorporating the transparent perovskite top cell will be introduced.

Peroxiredoxin5 (Prdx5), a thioredoxin peroxidase, is an antioxidant enzyme that is widely studied for its antioxidant properties and protective roles in neurological and cardiovascular disorders. This study is aimed at investigating the functional significance of Prdx5 in mitochondria and at analyzing its roles in ciliogenesis during the process of vertebrate development.We found that several Prdx genes were strongly expressed in multiciliated cells in developing Xenopus embryos, and their peroxidatic functions were crucial for normal cilia development. Depletion of Prdx5 increased levels of cellular reactive oxygen species (ROS), consequently leading to mitochondrial dysfunction and abnormal cilia formation. Proteomic and transcriptomic approaches revealed that excessive ROS accumulation on Prdx5 depletion subsequently reduced the expression level of pyruvate kinase (PK), a key metabolic enzyme in energy production. We further confirmed that the promotor activity of PK was significantly reduced on Prdx5 depletion and that the reduction in PK expression and its promoter activity led to ciliary defects observed in Prdx5-depleted cells.Our data revealed the novel relationship between ROS and Prdx5 and the consequent effects of this interaction on vertebrate ciliogenesis. The normal process of ciliogenesis is interrupted by the Prdx5 depletion, resulting in excessive ROS levels and suggesting cilia as vulnerable targets of ROS.Prdx5 plays protective roles in mitochondria and is critical for normal cilia development by regulating the levels of ROS. The loss of Prdx5 is associated with excessive production of ROS, resulting in mitochondrial dysfunction and aberrant ciliogenesis.

Background/Aims: Many gastrointestinal (GI) endoscopic procedures are difficult and cumbersome owing to the limitation of currently available endoscopic devices. This study aimed to develop an endoscopic guidetube for multipurpose endoscopic procedures and assess its use in a realistic GI endoscopic simulator. Methods: The guidetube used is a soft overtube composed of neoprene and is designed to assist various endoscopic procedures on demand. In total, 15 types of procedures were performed in GI simulators. Four procedures were performed in the stomach model and 11 in the colon model. The procedures include repeated endoscopic insertion and foreign body removal in various positions. The mean insertion and procedure time were assessed in each session. All procedures were performed by 5 expert endoscopists. Results: Endoscopic procedures with the new guidetube were faster and more effective than the conventional endoscopic techniques. The mean insertion time of the endoscope with the guidetube was significantly shorter than that without the guidetube. The guidetube was safely inserted without scratch using low pushing force. Objects of various sizes larger than the endoscopic channel were easily removed by the guidetube-assisted endoscopic procedures. Conclusions: This preliminary study shows that guidetube-assisted endoscopic procedures are faster, easier, safer and cheaper than conventional endoscopic procedures. Clin Endosc 2019;52:247-251

The mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid, on steatohepatitis. We performed comparative proteomic analysis using methionine and choline-deficient (MCD) diet-induced NASH model mice. Eighteen proteins were identified from the two-dimensional proteomic analysis, which are not only differentially expressed, but also significantly improved, by silibinin treatment. Interestingly, seven of these proteins, including keratin cytoskeletal 8 and 18, peroxiredoxin-4, and protein disulfide isomerase, are known to undergo GlcNAcylation modification, most of which are related to structural and stress-related proteins in NASH model animals. Thus, we primarily focused on how the GlcNAc modification of these proteins is involved in the progression to NASH. Remarkably, silibinin treatment alleviates the severity of hepatic inflammation along with O-GlcNAcylation in steatohepatitis. In particular, the reduction of inflammation by silibinin is due to the inhibition of the O-GlcNAcylation-dependent NF-&kappa, B-signaling pathway. Therefore, silibinin is a promising therapeutic agent for hyper-O-GlcNAcylation as well as NASH.

Background The guidelines for applying individual adjustments to macaques according to the severity of behavioral symptoms during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment were provided to reproduce stable chronic Parkinsonism in a recent study (Potts et al., 2014). But, since there are insufficient guidelines regarding objective severity criteria of individual symptoms for adjustments of MPTP treatment, it is difficult to develop MPTP-induced chronic non-human primate (NHP) models with stable symptoms. New method The individual adjustments of MPTP administration based on results of automatic quantification of global activity (GA) using a video-based tracking system were applied to develop MPTP-PD model. Low-dose (0.2 mg/kg) intramuscular injection was repeated continuously until GA was lower than 8% of baseline Parkinsonian behavior scores. The positron emission tomography imaging were used to follow the longitudinal course of Parkinson’s disease (PD). Results Significant reductions in GA and dopamine transporter activity, along with significant increases in Parkinsonian behavior scores were found from 4 to 48 weeks following the first administration. GA was correlated with the Parkinsonian behavior score. The dopamine transporter activity was correlated with GA and the Parkinsonian behavior score. However, it was not correlated with the total dose of MPTP. Damage of dopaminergic neuronal systems in the basal ganglia was confirmed by immunohistochemistry and Western blot. Comparison with existing method This study reinforces previous guidelines regarding production of NHP models with stable Parkinsonian symptoms. Conclusions This novel strategy of MPTP administration based on global activity evaluations provides an important conceptual advance for the development of chronic NHP Parkinsonian models.

Osteoclasts (OCs) are resorptive cells responsible for bone erosion in diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Montelukast is a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist clinically used for the treatment of asthma. In the present study, the role of CysLTR1 on OC formation and bone loss was investigated using montelukast. Montelukast inhibited receptor activator of nuclear factor‑κB ligand (RANKL)‑induced OC formation in cultures of mouse bone marrow macrophages. Additionally, montelukast suppressed actin ring formation and bone resorption activity of differentiated OCs. The inhibitory effect of montelukast was associated with impaired activation of extracellular signal‑regulated kinase, AKT serine/threonine kinase, and/or phospholipase Cγ2 signaling pathways downstream of RANK, followed by decreased expression of nuclear factor of activated T cells c1. Notably, OC formation was efficiently restored by addition of adenosine diphosphate, a P2Y12 agonist, as well as by addition of CysLT. Furthermore, similar to montelukast, P2Y12 blockade by a pharmacological inhibitor or siRNAs suppressed OC differentiation. These data indicate the involvement of the P2Y12 receptor in the inhibitory effect of montelukast on osteoclastogenesis. In vivo, montelukast significantly inhibited inflammation‑induced osteoclastogenesis in the calvarial model. Montelukast also served a protective role in a murine ovariectomy (OVX)‑ and unloading‑induced bone loss model. Altogether, these results confirmed that the CysLTR1 antagonist exerted an inhibitory effect on OC formation in vitro and in vivo. It may be useful for the treatment of bone diseases associated with excessive bone resorption.

The mechanisms underlying the progression to non-alcoholic steatohepatitis (NASH) remain to be elucidated. In the present study, we aimed to identify the proteins involved in the pathogenesis of liver tissue inflammation and to investigate the effects of silibinin, a natural polyphenolic flavonoid, on steatohepatitis. We performed comparative proteomic analysis using methionine and choline-deficient (MCD) diet-induced NASH model mice. Eighteen proteins were identified from the two-dimensional proteomic analysis, which are not only differentially expressed, but also significantly improved, by silibinin treatment. Interestingly, seven of these proteins, including keratin cytoskeletal 8 and 18, peroxiredoxin-4, and protein disulfide isomerase, are known to undergo GlcNAcylation modification, most of which are related to structural and stress-related proteins in NASH model animals. Thus, we primarily focused on how the GlcNAc modification of these proteins is involved in the progression to NASH. Remarkably, silibinin treatment alleviates the severity of hepatic inflammation along with O-GlcNAcylation in steatohepatitis. In particular, the reduction of inflammation by silibinin is due to the inhibition of the O-GlcNAcylation-dependent NF-κB-signaling pathway. Therefore, silibinin is a promising therapeutic agent for hyper-O-GlcNAcylation as well as NASH.

Background Patients who have undergone curative surgery for stage I lung cancer require continued surveillance owing to the risk of a second primary lung cancer developing. Early diagnosis allows for prompt intervention. However, as in primary cancers, the role of wedge vs lobar resections remains controversial. Methods The Surveillance Epidemiology and End Results database was examined from 2004 to 2012 and all pathologically proven stage I lung cancer patients who underwent cancer-directed surgery were selected. Cases in which a second primary lung cancer developed 6 or more months after diagnosis of the first cancer were analyzed for survival after surgical treatment. Results Second primary lung cancer was identified in 625 patients, of whom 331 (53%) were diagnosed with stage I disease; 43.8% of patients underwent surgery alone, 30.9% received radiation alone, and 21.0% received neither surgery nor radiation. Of the patients who underwent surgery, 57.7% received wedge resection and 36.5% received a lobectomy. Surgical intervention was a positive predictor of survival—both wedge resection and lobectomy exhibited improved outcomes vs no surgery—but there was no statistically significant difference between the two surgical modalities. Conclusions Wedge and lobar resections demonstrate similar survival for second primary lung cancers.

Iron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca2+, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood. In this study, we demonstrated that iron overload induces ROS production earlier in the ER than in the mitochondria, and peroxiredoxin 5 (Prx5), which is a kind of antioxidant induced by iron overload, prevents iron overload-induced mitochondrial fragmentation mediated by contact with ER and translocation of Drp1, by inhibiting ROS production and calcium/calcineurin pathway in HT-22 mouse hippocampal neuronal cells. Moreover, Prx5 also prevented iron overload-induced ER-stress and cleavage of caspase-3, which consequently attenuated neuronal cell death. Therefore, we suggested that iron overload induces oxidative stress in the ER earlier than in the mitochondria, thereby increasing ER stress and calcium levels, and consequently causing mitochondrial fragmentation and neuronal cell death. So we thought that this study is essential for understanding iron toxicity in neurons, and Prx5 may serve as a new therapeutic target to prevent iron overload-induced diseases and neurodegenerative disorders.

Objectives Esophageal cancer (EC) black patients have higher mortality rates than Whites. The lower rate of surgery in Blacks may explain the survival difference. We explored the Surveillance Epidemiology and End Results database to determine the impact of surgery on mortality in Blacks and Whites EC. Methods All cases of pathologically proven local and locoregional adenocarcinoma and squamous cell carcinoma of the esophagus from 1973 to 2011 were identified (13,678 White, 2,894 Black patients). Cervical esophageal cancer was excluded. Age, sex, diagnosis year, stage, cancer-directed surgery, radiation, and vital status were analyzed according to self-reported race. Results Blacks had higher 1-year mortality, adjusted for age, sex, stage, year of diagnosis, histology, and therapy [adjusted hazard ratio (HRadj): 1.24 (95% CI 1.16–1.32)]. Undergoing surgery was an independent predictor of improved survival overall (HRadj 0.30, 95% CI 0.27–0.33). Black patients treated surgically experienced significantly lower survival than Whites, but the difference was not observed in those who did not undergo surgery. Conclusions Although surgery appears to reduce mortality overall, early survival is worse for Blacks. Investigation into racial disparities in health care access and delivery, and to skilled esophageal surgeons is warranted to improve survival for all patients, particularly Blacks. J. Surg. Oncol. 2016;113:659–664. © 2016 Wiley Periodicals, Inc.

Aims Leydig cells are characterized by their ability to produce testosterone. When the Leydig cells are unable to produce enough testosterone, spermatogenesis fails completely. Considering this, it is of great interest to investigate whether the expressions of steroidogenic enzymes are affected by testicular heat stress. This study aimed to demonstrate that heat induced ER-stress significantly influences steroidogenic enzyme expression and testosterone production in the Leydig cells. Main methods C57BL/6 mice were subjected to repetitive testicular heat-treatment at 42 °C for 15 min per day, and heat-treated mLTC-1 cells following hCG treatment for 1 h. The protein and RNA expressions were measured by Western blot, RT-PCR. The testosterone and progesterone levels were detected by EIA. The histological and pathological characteristics using hematoxylin and eosin (H&E) and antibody stains. Key findings The 3β-HSD expression was decreased by heat-stress and hCG treatment. While the GRP78/BiP and CHOP levels were increased by ER-stress inducers, those of the steroidogenic enzyme and progesterone were decreased. In contrast, an ER-stress inhibitor rescued the testosterone levels, even under heat-stress conditions. Moreover, the Leydig cells were randomly scattered, and severely damaged upon repetitive testicular heat-treatment. Additionally, immunohistochemical analyses revealed that cleaved caspase-3 was elevated in the testicular Leydig cells, and rescued by TUDCA. Thus, repetitive testicular heat-treatment in mice promotes excessive ER-stress, thereby leading to apoptosis of the Leydig cells and thus, decreased testosterone production. Significance Our findings help to provide an ER-stress mediate mechanistic explanation to the impairment of spermatogenesis upon elevation of the testicular temperature.

Alzheimer's disease (AD), a neurodegenerative disorder, is caused by amyloid-beta oligomers (AβOs). AβOs induce cell death by triggering oxidative stress and mitochondrial dysfunction. A recent study showed that AβO-induced oxidative stress is associated with extracellular signal-regulated kinase (ERK)-dynamin related protein 1 (Drp1)-mediated mitochondrial fission. Reactive oxygen species (ROS) are regulated by antioxidant enzymes, especially peroxiredoxins (Prxs) that scavenge H2O2. These enzymes inhibit neuronal cell death induced by various neurotoxic reagents. However, it is unclear whether Prx5, which is specifically expressed in neuronal cells, protects these cells from AβO-induced damage. In this study, we found that Prx5 expression was upregulated by AβO-induced oxidative stress and that Prx5 decreased ERK-Drp1-mediated mitochondrial fragmentation and apoptosis of HT-22 neuronal cells. Prx5 expression was affected by AβO, and amelioration of oxidative stress by N-acetyl-L-cysteine decreased AβO-induced Prx5 expression. Prx5 overexpression reduced ROS as well as RNS and apoptotic cell death but Prx5 knockdown did not. In addition, Prx5 overexpression ameliorated ERK-Drp1-mediated mitochondrial fragmentation but Prx5 knockdown did not. These results indicated that inducible Prx5 expression by AβO plays a key role in inhibiting both ERK-Drp1-induced mitochondrial fragmentation and neuronal cell death by regulating oxidative stress. Thus, Prx5 may be a new therapeutic agent for treating AD.

Current touch pen requires the special equipments to detect a touch and its price increases in proportion to the screen size. In this paper, we propose a method for detecting a touch and implementing a pen using the depth information. The proposed method obtains a background depth image using a depth camera and extracts an object by comparing a captured depth image with the background depth image. Also, we determine a touch if the depth value of the object is the same as the background and then provide the pen event. Using this method, we can implement a cheaper and more convenient touch pen.

Exterior venetian blinds (EVBs) are widely used in commercial and residential buildings, and show a high performance level for both shading and lighting purposes. However, an EVB installed over an open window also influences natural ventilation rates. In this study, applying the pressure loss rate of an EVB to wind-driven natural ventilation rates was proposed. A mock-up building was set that the EVB was installed on the front opening. Wind generator was installed toward the front opening in order to describe wind-driven cross ventilation in a single zone. To investigate wind pressure changes through the EVB plane, 16 pressure measuring taps were installed on each of the front and back side of the EVB plane. Various wind speeds were induced toward the front opening so as to derive the pressure loss rate for the four EVB slat angle cases (0°, 45°, 90°, and no shading). The pressure loss rates for each case were derived from the field measurements. The results show that the pressure loss rates have a range of 0.22 to 0.90. In addition, the measurement results indicated that an EVB can change the air velocity by about 50% based on the slat angle. Therefore, when an EVB is installed on a window opening, the effect of the EVB on wind-driven cross ventilation rate should be taken into account.

Perfluoroalkyl compounds (PFCs) are globally distributed synthetic compounds that are known to adversely affect human health. Developmental toxicity assessment of PFCs is important to facilitate the evaluation of their environmental impact. In the present study, we assessed the developmental toxicity and teratogenicity of PFCs with different numbers of carbon atoms on Xenopus embryogenesis. An initial frog embryo teratogenicity assay-Xenopus (FETAX) assay was performed that identified perfluorohexanoic (PFHxA) and perfluoroheptanoic (PFHpA) acids as potential teratogens and developmental toxicants. The mechanism underlying this teratogenicity was also investigated by measuring the expression of tissue-specific biomarkers such as phosphotyrosine‑binding protein, xPTB (liver); NKX2.5 (heart); and Cyl18 (intestine). Whole‑mount in situ hybridization, reverse transcriptase‑polymerase chain reaction (RT-PCR), and histologic analyses detected severe defects in the liver and heart following exposure to PFHxA or PFHpA. In addition, immunoblotting revealed that PFHpA significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PFHxA slightly increased these, as compared with the control. These results suggest that PFHxA and PFHpA are developmental toxicants and teratogens, with PFHpA producing more severe effects on liver and heart development through the induction of ERK and JNK phosphorylation.

Reactive oxygen species (ROS) produced in biological reactions have been shown to contribute to ovarian aging. Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that protects cells by scavenging ROS; however, its effect on age-related, oxidative stress-associated ovarian failure has not been reported. Here, we investigated its role in age-related ovarian dysfunction and 4-vinylcyclohexene diepoxide (VCD)-induced premature ovarian failure using Prx2-deficient mice. Compared to those in wildtype (WT) mice, serum levels of anti-Mullerian hormone, 17β-estradiol, and progesterone and numbers of follicles and corpora lutea were significantly lower in 18-month-old Prx2-/- mice. Moreover, levels of Bax, cytochrome c, cleaved caspase-3, and phosphorylated JNK proteins were higher and numbers of apoptotic (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive) cells were considerably greater in 18-month-old Prx2-/- ovaries than WT ovaries. Furthermore, the effects of the ovarian toxicant VCD in significantly enhancing ROS levels and apoptosis through activation of JNK-mediated apoptotic signaling were more pronounced in Prx2-/- than WT mouse embryonic fibroblasts. Expression of the steroidogenic proteins StAR, CYP11A1, and 3β-HSD and serum levels of 17β-estradiol and progesterone were also reduced to a greater extent in Prx2-/- mice than WT mice after VCD injection. This reduced steroidogenesis was rescued by addition of the Prx mimic ebselen or JNK inhibitor SP600125. This constitutes the first report that Prx2 deficiency leads to acceleration of age-related or VCD-induced ovarian failure by activation of the ROS-induced JNK pathway. These findings suggest that Prx2 plays an important role in preventing accelerated ovarian failure by inhibiting ROS-induced JNK activation.

Elevated levels of reactive oxygen species (ROS) are a hallmark of obesity. Peroxiredoxin 5 (Prx5), which is a cysteine-dependent peroxidase enzyme, has an intensive ROS scavenging activity because it is located in the cytosol and mitochondria. Therefore, we focused on the role of Prx5 in regulating mitochondrial ROS and adipogenesis. We demonstrated that Prx5 expression was upregulated during adipogenesis and Prx5 overexpression suppressed adipogenesis by regulating cytosolic and mitochondrial ROS generation. Silencing Prx5 promoted preadipocytes to differentiate into adipocytes accumulating lipids by activating adipogenic protein expression. Prx5-deletion mice fed on a high-fat diet (HFD) exhibited significant increase in body weight, enormous fat pads, and adipocyte hypertrophy in comparison to wild type mice. Prx5 deletion also remarkably induced adipogenesis-related gene expression in white adipose tissue. These phenotypic changes in Prx5-deletion mice were accompanied with lipid metabolic disorders, such as excessive lipid accumulation in the liver, severe hepatic steatosis, and high levels of triglyceride in the serum. These results demonstrated that Prx5 deletion increased the susceptibility to HFD-induced obesity and several of its associated metabolic disorders. In conclusion, we suggest that Prx5 inhibits adipogenesis by modulating ROS generation and adipogenic gene expression, implying that Prx5 may serve as a potential strategy to prevent and treat obesity.

Additional file 2: Fig. S2. Transcriptome analysis revealed that KDM5C is essential for Xenopus embryonic development. We performed RNA-seq and analyzed groups of genes that are essential for several biological processes. The downregulation of specific genes by kdm5c knockdown indicated that KDM5C plays significant roles in organ development and structure morphogenesis.

Figure S2. Effects of PRDX1 on progesterone production in CL tissue using Prdx1 heterozygous and K/O mice. We observed ovary morphology in wild type, Prdx1 K/O and heterozygous mice (A). Serum progesterone levels were measured using a progesterone kit in Prdx1 K/O and heterozygous mice (B). The levels of steroidogenic enzymes 3β-HSD and P450SSC were determined in the CL tissue using western blot analysis. The relative levels of the steroidogenic enzymes were normalized to β-actin levels (C). Western blotting analysis of the ER stress marker CHOP in CL tissue of Prdx1 heterozygous and K/O mice. The relative levels of CHOP were normalized to β-tubulin levels (control). (D) The histogram values of densitometry analysis were obtained using the Image J software. The bar graphs represent the least-squares means ± SEM of three independent experiments. *P

Figure S1. Changes in PRDX family (2–6) protein levels in luteal phase of WT mice. Protein levels of PRDX 2–6 were confirmed in CL tissue by western blot analysis (A). The relative levels of PRDX proteins were obtained after normalization to β-actin levels. The histogram values of densitometry analysis were obtained using the Image J software. The bar graph data represent the least-squares means ± SEM of three independent experiments. *P

In this paper, we propose a method for correction of perspective distortion on a taken image. An image taken by a camera is caused perspective distortion depending on the direction of the camera when objects are projected onto the image. The proposed method in this paper is to obtain the normal vector of the plane through the depth information using a depth camera and calculate the direction of the camera based on this normal vector. Then the method corrects the perspective distortion to the view taken from the front side by performing a rotation transformation on the image according to the direction of the camera. Through the proposed method, it is possible to increase the processing speed than the conventional method such as correction of perspective distortion based on color information.

Non-Hodgkin lymphoma involving the esophagus is very rare. Only a few cases have been reported in the English literature to date, and it accounts for less than 1% of all cases of gastrointestinal lymphoma. As this malignancy manifests as a submucosal tumor, pathological diagnosis by using a simple endoscopic biopsy alone is difficult. Therefore, surgical biopsy, endoscopic mucosal resection, and endoscopic ultrasound-guided fine-needle aspiration have been used in most cases. Herein, we report a case of esophageal mucosa-associated lymphoid tissue lymphoma in a 49-year-old man, which involved the use of a stacked forceps biopsy to obtain adequate samples for pathological analysis; the use of the stacked forceps biopsy method is unlike those used in previous cases. The patient received cyclophosphamide, vincristine, and prednisolone chemotherapy; he achieved a complete response. In addition, we review the literature relevant to this case.

Mitochondrial dysfunction is implicated in age-related degenerative disorders such as Alzheimer's disease (AD). Maintenance of mitochondrial dynamics is essential for regulating mitochondrial function. Aβ oligomers (AβOs), the typical cause of AD, lead to mitochondrial dysfunction and neuronal loss. AβOs have been shown to induce mitochondrial fragmentation, and their inhibition suppresses mitochondrial dysfunction and neuronal cell death. Oxidative stress is one of the earliest hallmarks of AD. Cyclin-dependent kinase 5 (Cdk5) may cause oxidative stress by disrupting the antioxidant system, including Prx2. Cdk5 is also regarded as a modulator of mitochondrial fission; however, a precise mechanistic link between Cdk5 and mitochondrial dynamics is lacking. We estimated mitochondrial morphology and alterations in mitochondrial morphology-related proteins in Neuro-2a (N2a) cells stably expressing the Swedish mutation of amyloid precursor protein (APP), which is known to increase AβO production. We demonstrated that mitochondrial fragmentation by AβOs accompanies reduced mitofusin 1 and 2 (Mfn1/2) levels. Interestingly, the Cdk5 pathway, including phosphorylation of the Prx2-related oxidative stress, has been shown to regulate Mfn1 and Mfn2 levels. Furthermore, Mfn2, but not Mfn1, over-expression significantly inhibits the AβO-mediated cell death pathway. Therefore, these results indicate that AβO-mediated oxidative stress triggers mitochondrial fragmentation via decreased Mfn2 expression by activating Cdk5-induced Prx2 phosphorylation. Mitochondrial fragmentation induced by amyloid-beta oligomer (AβOs) which is generated from the Swedish mutation of amyloid precursor protein (APP) accompanies reduced Mfn1/2 levels. Interestingly, the Cdk5 pathway, including phosphorylation of the Prx2-related oxidative stress, has been shown to regulate Mfn1/2. Furthermore, Mfn2 over-expression significantly inhibits the AβO-mediated neuronal cells death pathway, but not Mfn1 over-expression. Therefore, these results indicate that AβO-mediated oxidative stress triggers mitochondrial fragmentation via decreased Mfn2 expression by activating Cdk5-induced Prx2 phosphorylation. ATP, adenosine triphosphate; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; Cdk5, Cyclin-dependent kinase; Cyt C, cytochrome C; Mfn2, mitofusin 2; Prx2, peroxiredoxin 2; ROS, reactive oxygen species.

Aims: Lipopolysaccharide (LPS) is considered a prominent pathogenic factor in inflammatory bone diseases. LPS challenge contributes to the production of reactive oxygen species (ROS) in diverse inflammatory diseases. However, its mechanism remains to be clarified in bone. Thus, we investigated the critical mechanism of ROS in LPS-induced osteoclastogenesis and bone loss. Results: Antioxidant prevented LPS-induced osteoclast formation via inhibition of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos expression in preosteoclasts. Moreover, LPS-induced osteoclast formation via ROS was attenuated by treatment with c-Jun N-terminal protein kinase (JNK) inhibitor. Interestingly, LPS also activated signal transducer and activator of transcription 3 (STAT3), which is suppressed by antioxidants. We found that knockdown of STAT3 or use of a STAT3 inhibitor resulted in a significant reduction in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and nitric oxide (NO) production, followed by decreased osteoclast formation by LPS. Peroxiredoxin II (PrxII) is a member of the antioxidant enzyme family, and it plays a protective role against oxidative damage caused by ROS. In our study, ROS production and osteoclast formation by LPS was significantly enhanced in PrxII−/− cells. Moreover, JNK-mediated c-Fos and NFATc1 expression was promoted in PrxII−/− cells. Furthermore, STAT3 activation and accompanying IL-1β, IL-6, and NO production was also increased in PrxII−/− cells. Consistent with the in vitro result, PrxII-deficient mice showed increased osteoclast formation and bone loss by LPS challenge compared with wild-type mice. Innovation: For the first time, we showed that LPS-induced ROS signaling is dependent on the coordinated mechanism of JNK and STAT3 during osteoclastogenesis, which is negatively regulated by PrxII. Conclusion: We suggest that PrxII could be useful in the development of a novel target for inflammatory bone loss. Antioxid. Redox Signal. 22, 63–77.

The energy performance of buildings depends on how effectively the building envelope responds to climate. Architects, therefore, need to design building envelopes with the consideration of local climate characteristics in the early design stage. Simplified formulas were used that evaluate the heating and cooling energy demand of building envelopes, which were applied to a model building with envelope and climate properties according to eight climate zones. Two climate indices, P and S , were developed. P enables the comparison of the heating and cooling energy demand of building envelopes, and S is for comparing the solar heat gain during heating and cooling seasons to review the feasibility of installing shading devices. The physical properties of envelopes were set differently according to the requirements in each climate zone proposed by American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE) 90.1. Using local climate data, the P and S of 24 cities over eight climate zones in the United States were derived, which can be used to evaluate the heating and cooling energy characteristics of envelopes. The indices not only enable users to understand the characteristics of the local climate conditions in a simple manner, but also to carry out quantitative assessments on whether shading devices are feasible and, if so, what type is recommended.

Background and Objectives Ergonovine stress echocardiography (ErgECHO) has been proposed as a noninvasive tool for the diagnosis of coronary vasospasm. However, concern over the safety of ErgECHO remains. This study was undertaken to investigate the safety and prognostic value of ErgECHO in a large population. Methods We studied 3,094 consecutive patients from a single-center registry who underwent ErgECHO from November 2002 to June 2009. Medical records, echocardiographic data, and laboratory findings obtained from follow-up periods were analyzed. Results The overall positive rate of ErgECHO was 8.6%. No procedure-related mortality or myocardial infarction (MI) occurred. Nineteen patients (0.6%) had transient symptomatic complications during ErgECHO including one who was successfully resuscitated. Cumulative major adverse cardiac events (MACEs) occurred in 14.0% and 5.1% of the patients with positive and negative ErgECHO results, respectively (p220 mg/dL, and positive ErgECHO result itself were independent factors associated with MACEs. Conclusions ErgECHO can be performed safely by experienced physicians and its positive result may be an independent risk factor for long-term adverse outcomes. It may also be an alternative tool to invasive ergonovine-provoked coronary angiography for the diagnosis of vasospastic angina.

Exterior dynamic shading devices, installed on “kinetic façades”, generate shaded areas of various shapes on windows according to the shape of the shading elements and the direction of their movement. The calculation of the shaded area is vitally important because it is directly related to the solar heat gain calculation process in building energy assessments. This paper dis-cusses a dynamic calculation method for deriving shaded fractions in consideration of the irregular shapes and unique movements of the shading elements in kinetic façades. The planar-polygon method was adopted for calculating accurate shaded areas on a window generated by irregularly shaped shade elements. To account for movements of the shading elements, the range of movement directions (i.e., rotating, sliding, etc.) was divided into steps of equivalent intervals. Applying these two methods, a shaded area calculation tool for the kinetic façade was developed. Three movement directions of shading devices were chosen for calculating shaded area, and the values of shaded fractions for six kinetic façade types were derived for different façade orientations during the summer and winter solstices. Lastly, to simplify the detailed calculation method, estimation equations for two types of kinetic façade were derived from a trend analysis of the shaded fraction values. This study deals with both detailed and simplified methods (estimation equation) for deriving the shaded fraction. The detailed method can be a more accurate solution in deriving the shaded fractions generated by complex exterior movable shading devices. However, the simplified method can be adopted in the early design stages to review various shading devices within a brief duration of time.

Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function.Pretreatment of chrysophanol in BV-2 murein microglial cells was carried out for 1 hour, followed by stimulation with 1 μg/mL LPS. Level of proteins and RNAs were detected by western blotting and Reverse Transcriptase PCR. DsRed2-Mito-expressing cells were used for detecting mitochondrial morphology.In this study, we determined the effects of chrysophanol on lipopolysaccharide (LPS)-induced microglial activation. Chrysophanol inhibited the LPS-induced production of proinflammatory mediators and cytokines via suppression of mitogen-activated protein kinase/nuclear factor kappa-B activation and reactive oxygen species generation. In addition, chrysophanol downregulated LPS-induced mitochondrial fission by diminishing dynamin-related protein 1 (Drp1) dephosphorylation. Taken together, chrysophanol suppressed the proinflammatory response of activated microglia via inhibition of Drp1-dependent mitochondrial fission.Our findings can provide the basis for the use of chrysophanol in microglial inflammatory response-mediated neurodegenerative diseases. Furthermore, our study can contribute to the production of new drugs for inflammatory response-mediated neurodegenerative diseases by purification of chrysophanol.

Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells. The exposure of the glutamate treatment caused neuronal cell death through an alteration of Bax/Bcl-2 expression and translocation of mitochondrial apoptosis-inducing factor (AIF) to the cytoplasm of HT-22 cells. In addition, glutamate induced an increase in dephosphorylation of dynamin-related protein 1 (Drp1), mitochondrial fragmentation, and mitochondrial dysfunction. The pretreatment of Ole decreased Bax expression, increased Bcl-2 expression, and inhibited the translocation of mitochondrial AIF to the cytoplasm. Furthermore, Ole amended a glutamate-induced mitochondrial dynamic imbalance and reduced the number of cells with fragmented mitochondria, regulating the phosphorylation of Drp1 at amino acid residue serine 637. In conclusion, our results show that Ole has a preventive effect against glutamate-induced toxicity in HT-22 hippocampal neuronal cells. Therefore, these data imply that Ole may be an efficient approach for the treatment of neurodegenerative diseases.

Inflammatory bowel disease (IBD) is a group of chronic, relapsing, immunological, inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It has been reported that UC, which is studied using a dextran sodium sulfate (DSS)-induced colitis model, is associated with the production of reactive oxygen species (ROS) and the apoptosis of intestine epithelial cells (IEC). Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) has been reported as an essential enzyme in the mitochondrial antioxidant system via generation of NADPH. Therefore, we evaluated the role of IDH2 in DSS-induced colitis using IDH2-deficient (IDH2-/-) mice. We observed that DSS-induced colitis in IDH2-/- mice was more severe than that in wild-type IDH2+/+ mice. Our results also suggest that IDH2 deficiency exacerbates PUMA-mediated apoptosis, resulting from NF-κB activation regulated by histone deacetylase (HDAC) activity. In addition, DSS-induced colitis is ameliorated by an antioxidant N-acetylcysteine (NAC) through attenuation of oxidative stress, resulting from deficiency of the IDH2 gene. In conclusion, deficiency of IDH2 leads to increased mitochondrial ROS levels, which inhibits HDAC activity, and the activation of NF-κB via acetylation is enhanced by attenuated HDAC activity, which causes PUMA-mediated apoptosis of IEC in DSS-induced colitis. The present study supported the rationale for targeting IDH2 as an important cancer chemoprevention strategy, particularly in the prevention of colorectal cancer., Graphical abstract fx1, Highlights • DSS-induced colitis model is associated with the production of ROS. • IDH2 is an essential enzyme in the mitochondrial antioxidant system. • IDH2-deficient mice have an increased susceptibility to DSS-induced colitis. • IDH2 deficiency exacerbates apoptosis through the PUMA/NF-κB/HDAC axis. • Protection of NAC against DSS-induced colitis IDH2-deficient mice was observed.

Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study was to analyze the role of Prx in regulating Cdk5 activation in AD.We found that of the six Prx subtypes, Prx5 was increased the most in cellular (N2a-APPswe cells) model of AD. Prx5 in the brain of APP (amyloid precursor protein) transgenic mouse (Tg2576) was more increased than a nontransgenic mouse. We evaluated Prx5 function by using overexpression (Prx5-WT), a mutation in the catalytic residue (Prx5-C48S), and knockdown. Increased neuronal death and Cdk5 activation by amyloid beta oligomer (AβO) were rescued by Prx5-WT expression, but not by Prx5-C48S or Prx5 knockdown. Prx5 plays a role in Cdk5 regulation by inhibiting the conversion of p35 to p25, which is increased by AβO accumulation. Prx5 is also upregulated in both the cytosol and mitochondria and it protects cells from AβO-mediated oxidative stress by eliminating intracellular and mitochondrial reactive oxygen species. Moreover, Prx5 regulates Ca

Dysregulation of the production of pro-inflammatory mediators in microglia exacerbates the pathologic process of neurodegenerative disease. ROS actively affect microglia activation by regulating transcription factors that control the expression of pro-inflammatory genes. However, accurate information regarding the function of ROS in different subcellular organelles has not yet been established. Here, we analyzed the pattern of cytosolic and mitochondrial H