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Targeted therapy at the molecular level is important for pancreatic cancer treatment. This study looked over the anticancer activity of Orostachys japonicus in a human pancreatic cancer cell line, PANC‐1. An ethyl acetate fraction containing quercetin, kaempferol, and flavonol glycosides from O. japonicus (OJE) exhibited significant anticancer activity against the PANC‐1. OJE activated caspase‐3, caspase‐8, and caspase‐9, leading to the induction of both intrinsic and extrinsic apoptosis pathways. It also inhibited cyclin D1, cyclin B1, and cyclin‐dependent kinase 4, representing cell cycle arrest at both G1/S and G2/M phases. In addition, OJE phosphorylated MAPKs such as p38, JNK, and ERK, which are important upstream signaling factors in apoptosis and arrest of cell cycle inducing system. In conclusion, OJE effectively exerted antipancreatic cancer activity via induction of apoptosis directed by both intrinsic and extrinsic pathways and arrest of cell cycle regulated at both G1/S and G2/M stages, which is activated by MAPKs, p38, JNK, and ERK.

Among the many factors that promote cellular senescence, reactive oxygen species (ROS) are a focus of intense research because of their critical role in accelerating cellular senescence and initiating senescence-related diseases that can be fatal. Therefore, maintaining the proper balance of ROS in cells is a key method to alleviate senescence. Recent studies have found that isocitrate dehydrogenase 2 (IDH2), a critical enzyme of the tricarboxylic acid cycle, participates in ROS generation and in cellular dysfunction that is induced by excessive levels of ROS. Loss of IDH2 induces mitochondrial dysfunction that promotes excessive ROS generation and the development of several diseases. The results of this study suggest that Idh2 plays an important role in cellular senescence. Idh2 deficiency resulted in senescence-associated phenotypes and increased levels of senescence marker proteins in mouse embryonic fibroblasts and tissues. Furthermore, excessive ROS were generated in Idh2-deficient conditions, promoting cellular senescence by inducing cell cycle arrest through cyclin-dependent kinase 2. These results indicate that loss of Idh2 is a critical factor in regulating cellular senescence. Taken together, our findings contribute to the field of senescence research and suggest that IDH2 is a potential target of future anti-senescence studies.

Human pyridoxal 5'-phosphate phosphatase (PLPP), also known as a chronophin, is a phosphatase belonging to subfamily II of the HAD phosphatases, characterized by a large cap domain. As a member of the subfamily, its cap-open conformation is expected for substrate binding. We determined apo and PLP-bound PLPP/chronophin structures showing a cap-closed conformation. The active site, in which a PLP molecule was found, is too small to accommodate a phospho-cofilin peptide, the substrate of chronophin. A conformational change to a cap-open conformation may be required for substrate binding. The core and cap domains are joined through linker peptide hinges that change conformation to open the active site. The crystal structures reveal that a disulphide bond between the cap and core domains restricts the hinge motion. The enzyme displays PLP dephosphorylation activity in the cap-closed conformation with the disulphide bond and even in the crystal state, in which repositioning of the cap and core domains is restricted. Structural analysis suggests that a small substrate such as PLP can bind to the active site through a small movement of a local motif. However, a change to the cap-open conformation is required for binding of larger substrates such as phosphopeptides to the active site.

Monolithic perovskite/Si tandem solar cells have attracted particular interest because of the potential to achieve high power conversion efficiencies. However, tandem cells require the use of textured Si substrates for efficient light harvesting, and conformal deposition of the perovskite absorption layer on textured Si substrates remains challenging. Here, we introduce a process to prepare a conformal methylammonium lead iodide (MAPbI3) film on the various substrates regardless of their morphologies via the electrodeposition followed by vapor reaction. First, PbO2 films were electrodeposited on the planar indium tin oxide/NiO substrates in aqueous electrolyte, with their thickness and grain size controlled by adjusting the potential and reaction time. XPS and XRD analyses confirmed that the PbO2 film was fully reduced to PbO by annealing under a reducing atmosphere. Finally, the PbO films were converted into conformal MAPbI3 via MAI vapor reaction for 25 min at 180 °C. We also demonstrated that the PbO2 films could be evenly deposited on textured Si/ITO substrates using pulsed electrodeposition and were then converted into conformal MAPbI3 using the same vapor reaction process. The proposed approach thus provides a novel route for the preparation of high-quality perovskite films on both planar and textured substrates. Keywords: Electrochemical deposition, Thermal vapor reaction, Kinetics, Perovskite

Alzheimer's disease (AD) is a neurodegenerative disorder caused by amyloid beta oligomers (AβO), which induce cell death by triggering oxidative stress and endoplasmic reticulum (ER) stress. Oxidative stress is regulated by antioxidant enzymes, including peroxiredoxins. Peroxiredoxins (Prx) are classified into six subtypes, based on their localization and cysteine residues, and protect cells by scavenging hydrogen peroxide (H2O2). Peroxiredoxin 4 (Prx4) is unique in being localized to the ER; however, whether Prx4 protects neuronal cells from AβO-induced toxicity remains unclear, although Prx4 expression is upregulated in AβO-induced oxidative stress and ER stress. In this study, we established HT-22 cells in which Prx4 was either overexpressed or silenced to investigate its role in AβO-induced toxicity. AβO-stimulation of HT-22 cells with overexpressed Prx4 caused decreases in both AβO-induced ROS and ER stress (followed by ER expansion). In contrast, AβO stimulation caused increases in both ROS and ER stress that were notably higher in HT-22 cells with silenced Prx4 expression than in HT-22 cells. Consequently, Prx4 overexpression decreased apoptotic cell death and ameliorated the AβO-induced increase in intracellular Ca2+. Therefore, we conclude that Prx4 has a protective effect against AβO-mediated oxidative stress, ER stress, and neuronal cell death. Furthermore, these results suggest that Prx4 may be a target for preventing AβO toxicity in AD. Graphical abstract .

Background/Aims We used 3-dimensional (3D) printing technology to create a new hemostasis simulator for the stomach and investigated its efficacy and realism in endoscopic hemostasis training. Methods A new stomach hemostasis simulator, with two hemostasis modules for hemoclipping and injection, was constructed using a 3D printer. Twenty-one endoscopists, including 11 first-year fellows (beginner group) and 10 faculty members (expert group), tested the performance of the simulator. We recorded and reviewed five training sessions and evaluated the simulator with questionnaires using a 7-point Likert scale. Results The mean evaluation score of the expert group was 6.3±0.5 for the hemoclipping module and 6.0±0.6 for the injection module. The expert group strongly agreed that endoscopic handling in the simulator was realistic and reasonable for hemostasis training. The mean procedure time for hemoclipping was 72.7±7.1 seconds for the beginner group and 19.7±1.2 seconds for the expert group. The mean procedure time for injection was 92.1±9.8 seconds for the beginner group and 36.3±2 seconds for the expert group. The procedure time of beginner group became shorter with repetition and was significantly lower by the fifth trial. Conclusions A new 3D-printed hemostasis simulator is capable of hemostasis training and can very effectively train beginners before they perform the procedure in patients with gastrointestinal bleeding.

Microglial activation is known to be an important event during innate immunity, but microglial inflammation is also thought to play a role in the etiology of neurodegenerative diseases. Recently, it was reported that autophagy could influence inflammation and activation of microglia. However, little is known about the regulation of autophagy during microglial activation. In this study, we demonstrated that mitochondrial fission-induced ROS can promote autophagy in microglia. Following LPS-induced autophagy, GFP-LC3 puncta were increased, and this was suppressed by inhibiting mitochondrial fission and mitochondrial ROS. Interestingly, inhibition of mitochondrial fission and mitochondrial ROS also resulted in decreased p62 expression, but Beclin1 and LC3B were unaffected. Taken together, these results indicate that ROS induction due to increased LPS-stimulated mitochondrial fission triggers p62 mediated autophagy in microglial cells. Our findings provide the first important clues towards understanding the correlation between mitochondrial ROS and autophagy. Abbreviations: Drp1; Dynamin related protein 1, LPS; Lipopolysaccharide, ROS; Reactive Oxygen Species, GFP; Green Fluorescent Protein, CNS; Central Nervous System, AD; Alzheimer’s Disease, PD; Parkinson’s Disease, ALIS; Aggresome-like induced structures, iNOS; inducible nitric oxide synthase, Cox-2; Cyclooxygenase-2, MAPK; Mitogen-activated protein kinase; SODs; Superoxide dismutase, GPXs; Glutathione Peroxidase, Prxs; Peroxiredoxins

A methodology for low-cycle fatigue (LCF) performance assessment of beam-to-column connections commonly used in current Japanese steel moment-resisting frames, such as welded flange-bolted web connections and welded connections with rectangular hollow section columns, is presented in this paper. The proposed assessment methodology is based on an empirical relationship between the number of cycles to failure and beam rotation amplitude obtained from a database of cyclic loading test results. In the empirical relationship, the effects of decreasing the moment transfer efficiency at the beam web-to-column connection due to the slip behavior of the bolts, the out-of-plane deformation of the column flange and the loss of web section due to the weld access hole are considered. The proposed approach can be applied to evaluate the comprehensive fatigue performance of current Japanese beam-to-column connections, considering the moment transfer efficiency of the beam web-to-column connection details and the steel grade.

In this work, the nanoflakes of Co(OH)2 have been grown successfully on a stainless steel (SS) substrate at an ambient temperature. The novel architecture, binder free synthesis and considerable capacitance of Co(OH)2 nanoflakes render them as a potential candidate to be used as an electrode material for supercapacitor application. It is observed that the different cathodic potentials have a dramatic impact on the growth mechanism of Co(OH)2 nanoflakes. The prepared thin films were subjected for their structural and morphological study using X-ray diffraction, field emission scanning electron microscope, energy dispersive X-ray spectroscopy, etc. The supercapacitive properties of Co(OH)2 nanoflakes have been studied using cyclic voltammetry, galvanostatic charge–discharge and electrochemical impedance spectroscopy techniques. The Co(OH)2 nanoflakes evaluated a maximum specific capacitance of 275 F g−1 for 5 mV s−1 in 1 M KOH.

In the present work, binder-free MnCo2O4 nanoflakes were prepared using a cost-effective potentiostatic mode of electrodeposition. Structural and microstructural features of the prepared MnCo2O4 samples were examined by different characterization techniques including X-ray diffraction, Raman, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy and supercapacitive testing. The morphological investigation revealed that a unique nanoflake-like structure with uniform morphology. The electrochemical properties of MnCo2O4 nanoflakes were investigated by cyclic voltammetry, galvanostatic charge discharge and electrochemical impedance spectroscopy. The maximum specific capacitance observed for the MnCo2O4 thin films was 585 F g−1 for a current density of 0.2 mA cm−2. Our results indicate that the MnCo2O4 electrode has potential for application in supercapacitors.

Background/aim Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. Materials and methods Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. Results Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of pro-apoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. Conclusion Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers.

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.

Short-term variability, spatial variability, and the vertical distribution of an intertidal macroalgal assemblage were examined on the coast of Barton Peninsula, Maxwell Bay, King George Island, Antarctica. Sampling was performed during the three austral summer seasons from November 2016 to January 2019. The sampling interval for short-term variability was 1–2 months. Sampling for spatial variability was performed at two sites 400 m apart. Eighteen algal species were identified, with 75% relative coverage of the predominant red Iridaea cordata and endemic brown Phaeurus antarcticus. Summer abundance can be described as a shift from I. cordata to P. antarcticus, and the change in color is intuitively presented using a contour plot for the first time. Short-term variation in the macroalgal assemblage showed 78.35% similarity between one month and 64.61% similarity between two months. The spatial variation analysis indicated 77.13% similarity between the assemblage at the two sites. If global warming continues, the algal population of this region is expected to expand. P. antarcticus, which is primarily found in the subtidal zone, is predicted to relocate southward or higher in the near future. Long-term monitoring of this research region, which is dominated by the two species, is warranted to determine the impact of global warming on the macroalgal assemblage.

Canines are useful in mammalian preclinical studies because they are larger than rodents and share many diseases with humans. Canine fetal fibroblast cells (CFFs) are an easily accessible source of somatic cells. However, they are easily driven to senescence and become unusable with continuous in vitro culture. Therefore, to overcome these deficiencies, we investigated whether tetracycline-inducible L-myc gene expression promotes self-renewal activity and tumorigenicity in the production of induced conditional self-renewing fibroblast cells (iCSFCs). Here, we describe the characterization of a new iCSFC line immortalized by transduction with L-myc that displays in vitro self-renewal ability without tumorigenic capacity. We established conditionally inducible self-renewing fibroblast cells by transducing CFF-3 cells with L-myc under the tetracycline-inducible gene expression system. In the absence of doxycycline, the cells did not express L-myc or undergo self-renewal. The iCSFCs had a fibroblast-like morphology, normal chromosome pattern, and expressed fibroblast-specific genes and markers. However, the iCSFCs did not form tumors in a soft agar colony-forming assay. We observed higher expression of three ES modules (core pluripotency genes, polycomb repressive complex genes (PRC), and MYC-related genes) in the iCSFCs than in the CFF-3 cells; in particular, the core pluripotency genes (OCT4, SOX2, and NANOG) were markedly up-regulated compared with the PRC and MYC module genes. These results demonstrated that, in canine fetal fibroblasts, L-myc tetracycline-inducible promoter-driven gene expression induces self-renewal capacity but not tumor formation. This study suggests that L-myc gene-induced conditional self-renewing fibroblast cells can be used as an in vitro tool in a variety of biomedical studies related to drug screening.

Background A large release of droplets is often expected around the periphery of the digestive endoscope insertion site. Therefore, a sense of alarm over infection because of droplets that may be released during digestive endoscopy examination is increasing. This study aimed to investigate the droplets released during digestive endoscopy using a high-speed camera. Methods We utilized a high-speed camera (FASTCAM SA-3, Photron Limited) capable of recording small, transparent droplets with a black background and high-brightness lighting. The obtained video files were analyzed using post-processing software. We divided the 20 models into the control (a spray bottle model and a cough model) and experimental groups (digestive endoscopy models). The sedative, proficiency of digestive endoscopy and the amount of gas injected were modulated to change the level of released droplets. Results For the control groups, droplets were clearly observed using a high-speed camera. However, no droplet larger than 10 µm in size was observed in the experimental groups. Furthermore, the changes in the sedative, proficiency of digestive endoscopy, and amount of gas injected did not affect droplet formation. Conclusions Based on high-speed camera photography, the risk of droplet generation during digestive endoscopy was not higher than that during violent expiratory events, such as coughing and sneezing. Supplementary Information The online version contains supplementary material available at 10.1007/s00464-021-08581-0.

The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia.Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non-small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site.New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy;Both open and minimally invasive lung resection for clinical early-stage lung cancer are associated with new or enlarging postoperative hiatal hernia, especially after resections involving the left lower lobe.

Manual scoring of sleep stages from polysomnography (PSG) records is essential to understand the sleep quality and architecture. Since the PSG requires specialized personnel, a lab environment, and uncomfortable sensors, non-contact sleep staging methods based on machine learning techniques have been investigated over the past years. In this study, we propose an attention-based bidirectional long short-term memory (Attention Bi-LSTM) model for automatic sleep stage scoring using an impulse-radio ultra-wideband (IR-UWB) radar which can remotely detect vital signs. Sixty-five young (30.0 ± 8.6 yrs.) and healthy volunteers underwent nocturnal PSG and IR-UWB radar measurement simultaneously; From 51 recordings, 26 were used for training, 8 for validation, and 17 for testing. Sixteen features including movement-, respiration-, and heart rate variability-related indices were extracted from the raw IR-UWB signals in each 30-s epoch. Sleep stage classification performances of Attention Bi-LSTM model with optimized hyperparameters were evaluated and compared with those of conventional LSTM networks for same test dataset. In the results, we achieved an accuracy of 82.6 ± 6.7% and a Cohen's kappa coefficient of 0.73 ± 0.11 in the classification of wake stage, REM sleep, light (N1+N2) sleep, and deep (N3) sleep which is significantly higher than the conventional LSTM networks (p < 0.01). Moreover, the classification performances were higher than those reported in comparative studies, demonstrating the effectiveness of the attention mechanism coupled with bi-LSTM networks for the sleep staging using cardiorespiratory signals.

Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1β. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.

Surgery is a mainstay of treatment allowing for debulking of tumor and expansion of the lung for improvement in median survival and quality of life for patients with malignant pleural mesothelioma (MPM). Although optimal surgical technique remains open for debate—extrapleural pneumonectomy (EPP) vs. pleurectomy/decortication (P/D)—minimally invasive surgery (VATS-P/D) remains underutilized in the management of MPM. We examined whether VATS-P/D is a feasible alternative to EPP and P/D. We evaluated the New York Statewide Planning and Research Cooperative System (SPARCS) from 2007–2017 to assess the short-term complications of EPP vs. P/D, including a subanalysis of open P/D vs. VATS-P/D. There were 331 patients with open surgery, 269 with P/D and 62 with EPP. There were 384 patients with P/D, 269 were open and 115 VATS. Rates of any complication were similar between EPP and P/D patients, but EPP had significantly higher rates of cardiovascular complications. After adjusting for confounders, those with a VATS approach were less likely to have any complication, compared to an open approach and significantly less likely to have a pulmonary complication. VATS-P/D remains a viable alternative to radical surgery in MPM patients allowing for improved short-term outcomes.

Aims Metabolic syndrome (MS) is a global health problem associated with an increased risk of diabetes mellitus (DM), cardiovascular disease (CVD), and cancer. Body composition parameters, including obesity, visceral adiposity, and sarcopenia contribute to the development of MS and CVD. Previous studies have investigated the association of individual body composition parameters with MS. Studies analyzing the association between multiple body composition parameters and MS have been rare. We aimed to investigate the association between MS and multiple body composition parameters, including obesity, visceral adiposity, and sarcopenia. Methods A total of 13,620 subjects who underwent voluntary routine checkups at the Health Care Center of our institution between October 2014 and December 2019 were enrolled. Only data from the first examination of subjects who underwent repeated checkups were included. Clinical and laboratory data were collected. Skeletal muscle mass and visceral fat area (VFA) were measured using bioelectrical impedance analysis. Appendicular skeletal muscle mass (ASM) was divided by body weight (in kg) and expressed as a percentage (calculated as, ASM% = ASM × 100/Weight). Data were compared between the groups based on obesity, VFA, and ASM%. Logistic regression analysis was performed to determine the risk of MS in each group. Results Body mass index and VFA were significantly higher in subjects with MS than in those without MS. ASM% was significantly lower in subjects with MS than in those without MS. Subjects with obesity, visceral adiposity, or sarcopenia had a higher prevalence of MS than those without. As the number of metabolic components increased from 0 to 5, we identified a decreasing trend of ASM% and an increasing trend of VFA and BMI (P for trend < 0.001 for all). In the paired analyses, all the three body composition parameters showed additive effects in predicting MS. In the logistic regression analysis, the three parameters were associated with an increased risk of MS after adjustment for age, sex, hypertension, DM, dyslipidemia, smoking, alcohol intake, and C-reactive protein. Conclusions Obesity, visceral adiposity, and sarcopenia showed additive effects on MS prediction. Subjects with obesity, visceral adiposity, or sarcopenia were significantly associated with the increased risk of MS after adjustment for multiple confounders. Increasing skeletal muscle and reducing visceral fat may be strategies for the prevention or treatment of MS.

Coronavirus Disease 2019 (COVID-19) has rapidly spread to all corners of the globe. Different diagnostic tools, such as Chest X-ray (CXR), lung ultrasound (LUS), and computerized tomography (CT), have been used to detect active pneumonic lesions associated with COVID-19 with their varying degrees of sensitivity and specificity. This study was undertaken to investigate the clinical characteristics of COVID-19 patients with a pneumonic lung lesion detected by CT that is not detected by CXR. A total of 156 COVID-19 patients hospitalized at three nationally designated South Korean hospitals with no active lesion detected by CXR but on clinical suspicion of pneumonia underwent the CT examination and were enrolled. Medical records, which included demographic and clinical features, including comorbidity, symptoms, radiological, and laboratory findings on admission, were reviewed and analyzed. The risk factors of pneumonia detected by CT for patients without an active lesion detected by CXR were investigated. Of the 156 patients without an active lesion detected by CXR, 35 (22.44%) patients were found to have pneumonia by CT. The patients with pneumonia defined by CT were older than those without (64.1 years vs. 41.2 years). Comorbidities such as hypertension, diabetes, cardiovascular disease, preexisting stroke, and dementia were more common among patients with pneumonia defined by CT than those without. Serum albumin level, C-reactive protein (CRP), stroke, and age &ge, 70 years were significantly associated with pneumonia defined by CT after adjustment for age. In multivariable regression analysis, serum albumin level (adjusted odds ratio (AOR) = 0.123, 95% CI = (0.035&ndash, 0.429)) and preexisting stroke (AOR = 11.447, 95% CI = (1.168&ndash, 112.220)) significantly and independently predicted pneumonia detection by CT. Our results suggest that CT scans should be performed on COVID-19 patients negative for a pneumonic lung lesion by CXR who are suspected to be pneumonic on clinical grounds. In addition, older patients with a lower albumin level and a preexisting stroke should be checked for the presence of pneumonia despite a negative CXR finding for an active lesion.

Electrocardiogram (ECG) is one of the most widely used physiological signal that provides fundamental health information. Conventional ECG uses gel-type ECG electrodes, however, the gel-type ECG electrode is inconvenient for long-term or daily-life ECG monitoring. Capacitive ECG sensor was implemented to overcome the shortcoming of gel-type ECG electrodes. The wireless power transfer (WPT) technology can improve ubiquitous healthcare, but the power consumption is an important factor of the system based on WPT. Previous study did not consider the power consumption of the system. In this study, we implemented a low-power capacitive ECG monitoring system. The supply power of the system was 5V, and Bluetooth low energy (BLE) module was applied to decrease the power consumption in wireless data transmission. The total power consumption of the system was 16.4 mW.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in women worldwide, with an overall 5 year survival rate below 30%. The low survival rate is associated with the persistence of cancer stem cells (CSCs) after chemotherapy. Therefore, CSC-targeting strategies are required for successful EOC treatment. Pan-human epidermal growth factor receptor 4 (HER4) and L-type calcium channels are highly expressed in ovarian CSCs, and treatment with the pan-HER inhibitor poziotinib or calcium channel blockers (CCBs) selectively inhibits the growth of ovarian CSCs via distinct molecular mechanisms. In this study, we tested the hypothesis that combination treatment with poziotinib and CCBs can synergistically inhibit the growth of ovarian CSCs. Combined treatment with poziotinib and manidipine (an L-type CCB) synergistically suppressed ovarian CSC sphere formation and viability compared with either drug alone. Moreover, combination treatment synergistically reduced the expression of stemness markers, including CD133, KLF4, and NANOG, and stemness-related signaling molecules, such as phospho-STAT5, phospho-AKT, phospho-ERK, and Wnt/&beta, catenin. Moreover, poziotinib with manidipine dramatically induced apoptosis in ovarian CSCs. Our results suggest that the combinatorial use of poziotinib with a CCB can effectively inhibit ovarian CSC survival and function.

Symptoms of Parkinson's disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed the alteration in Parkinsonian tremor signs and the functionality of presynaptic dopaminergic neuron using positron emission tomography imaging of dopamine transporters in these models. In addition, a significant inverse correlation between HDT and DAT level was identified, but no local bias was found. The correlation with intention tremor signs was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

Background Coronavirus disease 2019 (COVID-19) was first reported in December 2019 in China, and then it has disseminated worldwide. In Korea, a religious group-related super-spreading event triggered a sudden outbreak in Daegu city and Gyeongsangbuk-do in southeast Korea. This study was undertaken to document the clinical characteristics of patients hospitalized in Gyeongsangbuk-do. Methods Three hundred and fifty-two patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalized at Dongguk University Gyeongju Hospital or at the Andong Medical Center between February 18th and June 30th were enrolled in this study. Medical records were reviewed and demographic and clinical features, including comorbidities, symptoms, radiological and laboratory findings on admission were analyzed. In addition, we sought to identify risk factors of mortality. Results Mean age of the 352 study subjects was 56 years (range, 14–95). The mortality rate was 6.8% and mean age at death was 81 years (range, 57–91). The most common symptom was cough (31.8%) followed by a febrile sensation (28.4%), sputum (17.0%), sore throat (15.6%), and myalgia (13.1%). Eighty-one (23.0%) patients were asymptomatic, but a half of these patients exhibited pneumonic infiltration at presentation. Chest radiology showed no active lesion in 41.8% of the study subjects, bilateral pneumonia in 46.9%, and unilateral pneumonic infiltration in 11.4%. Among 24 patients that died, 18 subjects were transferred from a care facility. An age of ≥ 70 years, previous history of malignancy or diabetes, and fever (≥ 37.5°C) on admission were found to be significant risk factors of mortality. Conclusion Patients aged ≥ 70 years, those with fever on admission, and patients with an underlying malignancy or diabetes were found to be more likely to succumb to COVID-19. Elderly in care facilities or hospitalized patients with an underlying disease should receive more attention and be considered for preventive quarantine., Graphical Abstract

Studies have confirmed COVID-19 patients with diabetes are at higher risk of mortality than their non-diabetic counterparts. However, data-driven evidence of factors associated with increased mortality risk among hospitalized COVID-19 patients with diabetes is scarce in South Korea. This study was conducted to determine the mortality rate and identify risk factors of mortality among hospitalized COVID-19 patients with type 2 diabetes in Gyeongsangbuk-do province, South Korea. In this hospital-based, cross-sectional study, we enrolled a total of 324 patients with confirmed COVID-19, hospitalized at two of the tertiary level healthcare facilitates of Gyeongsangbuk-do, South Korea from 18 February to 30 June 2020. Demographic and clinical data and laboratory profiles were analyzed and multivariate logistic regression analysis was used to identify risk factors of mortality among diabetic patients with COVID-19. Of the 324 patients, 55 (16.97%) had diabetes mellitus. The mean age of all study subjects was 55 years, and the mean age of those with diabetes was greater than that of those without (69.8 years vs. 51.9 years). Remarkably, the mortality rate was much higher among those with diabetes (20.0% vs. 4.8%). Multivariate logistic regression analysis revealed that an older age (&ge, 70 years) and a high serum lactate dehydrogenase (LDH) levels significantly predicted mortality among hospitalized COVID-19 patients with diabetes. Our study cautions more attention to be paid to patients with diabetes mellitus hospitalized for COVID-19, especially those aged &ge, 70 years and those with a high serum LDH level, to reduce the risk of mortality.

Aberrant brain insulin signaling plays a critical role in the pathology of Alzheimer's disease (AD). Mitochondrial dysfunction plays a role in the progression of AD, with excessive mitochondrial fission in the hippocampus being one of the pathological mechanisms of AD. However, the molecular mechanisms underlying the progression of AD and mitochondrial fragmentation induced by aberrant brain insulin signaling in the hippocampal neurons are poorly understood. Therefore, we investigated the molecular mechanistic signaling associated with mitochondrial dynamics using streptozotocin (STZ), a diabetogenic compound, in the hippocampus cell line, HT-22 cells. In this metabolic dysfunctional cellular model, hallmarks of AD such as neuronal apoptosis, synaptic loss, and tau hyper-phosphorylation are induced by STZ. We found that in the mitochondrial fission protein Drp1, phosphorylation is increased in STZ-treated HT-22 cells. We also determined that inhibition of mitochondrial fragmentation suppresses STZ-induced AD-like pathology. Furthermore, we found that phosphorylation of Drp1 was induced by CDK5, and inhibition of CDK5 suppresses STZ-induced mitochondrial fragmentation and AD-like pathology. Therefore, these findings indicate that mitochondrial morphology and functional regulation may be a strategy of potential therapeutic for treating abnormal metabolic functions associated with the pathogenesis of AD.

Dynamin-related protein 1 (DRP1) is a mitochondrial membrane GTPase and regulates mitochondrial fission. In this study, we found that the cytokine RANKL increased the expression of DRP1 and its receptor proteins, Fis1, Mid49, and Mid 51, during osteoclast formation in mouse bone marrow-derived macrophages. Inactivation of the kinase GSK3β appeared to induce DRP1 expression. DRP1 knockdown or the DRP1 inhibitor Mdivi1 suppressed osteoclast differentiation via downregulation of c-Fos and NFATc1, the key transcription factor for osteoclast formation. Finally, the DRP1 inhibitor suppressed lipopolysaccharide-induced osteoclast formation in a calvarial model and ovariectomy-induced bone loss in vivo. Taken together, our data demonstrate that DRP1 positively contributes to RANKL-induced osteoclast differentiation by regulating the c-Fos-NFATc1 axis, suggesting the importance of mitochondrial DRP1 in osteoclastogenesis.

Understanding the agglomeration of cellulose derivatives is crucial for the production of instant gum-based food thickeners. In the present study, physical, rheological, and structural properties of agglomerated water-soluble cellulose gums (CGs), such as carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC), and methylcellulose (MC), were investigated at different concentrations of maltodextrin (MD) as a binder for fluidized-bed agglomeration. Among the CG agglomerates in the presence of MD, CMC exhibited better flowability and lower cohesiveness, showing lower Carr index and Hausner ratio values. The MC agglomerates with 20% MD exhibited higher porosity than the other CGs due to the size enlargement of MC particles, which was confirmed via scanning electron microscopy images and size distribution profiles. The dynamic moduli of the CG agglomerates were significantly decreased by the addition of MD and also decreased with increasing MD concentration. The tan δ values of the agglomerates increased with increasing MD concentration, indicating the enhancement of their viscous properties. These results suggest that the physical, rheological, and structural properties of cellulose derivatives with different types of CG can be greatly influenced by their agglomerate growths during fluidized-bed agglomeration of particles with the different concentrations of MD binder.

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

Alzheimer's disease (AD) is a neurodegenerative disease associated with the accumulation of amyloid-beta oligomers (AβO). Recent studies have demonstrated that mitochondria-specific autophagy (mitophagy) contributes to mitochondrial quality control by selectively eliminating the dysfunctional mitochondria. Mitochondria motility, which is regulated by Miro1, is also associated with neuronal cell functions. However, the role played by Miro1 in the mitophagy mechanism, especially relative to AβO and neurodegenerative disorders, remains unknown. In this study, AβO induced mitochondrial dysfunction, enhanced Parkin-mediated mitophagy, and reduced mitochondrial quantities in hippocampal neuronal cells (HT-22 cells). We demonstrated that AβO-induced mitochondrial fragmentation could be rescued to the elongated mitochondrial form and that mitophagy could be mitigated by the stable overexpression of Miro1 or by pretreatment with N-acetylcysteine (NAC)-a reactive oxygen species (ROS) scavenger-as assessed by immunocytochemistry. Moreover, using time-lapse imaging, under live cell-conditions, we verified that mitochondrial motility was rescued by the Miro1 overexpression. Finally, in hippocampus from amyloid precursor protein (APP)/presenilin 1 (PS1)/Tau triple-transgenic mice, we noted that the co-localization between mitochondria and LC3B puncta was increased. Taken together, these results indicated that up-regulated ROS, induced by AβO, increased the degree of mitophagy and decreased the Miro1 expression levels. In contrast, the Miro1 overexpression ameliorated AβO-mediated mitophagy and increased the mitochondrial motility. In AD model mice, AβO induced mitophagy in the hippocampus. Thus, our results would improve our understanding of the role of mitophagy in AD toward facilitating the development of novel therapeutic agents for the treatment of AβO-mediated diseases.

To date, researchers have developed various animal models of Alzheimer’s disease (AD) to investigate its mechanisms and to identify potential therapeutic treatments. A widely recognized model that mimics the pathology of human sporadic AD involves intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injections are an invasive approach, which creates limitations in generalizing the results. In this study, we produced a rodent model of AD using STZ (3 mg/kg) injection via the cisterna magna (CM) once every week for 4 weeks, and analyzed at 4 weeks and 16 weeks after final injection. In the CM-STZ rodent model of AD, we observed increase in extracellular amyloid-beta (Aβ) deposition and decrease and abnormal morphology of post-synaptic protein, PSD95 in 16 weeks STZ-injected group. The model developed using our less-invasive method induced features of AD-like pathology, including significantly increased extracellular amyloid-beta deposition, and decreased synaptic protein in the hippocampus. These findings supporting the success of this alternative approach, and thus, we suggest this is a promising, less invasive model for use in future AD research.

Picrasma quassioides (PQ) is a traditional Asian herbal medicine with anti-tumor properties that can inhibit the viability of HepG2 liver cancer cells. H-Ras is often mutated in liver cancer, however, the effect of PQ treatment on H-Ras mutated liver cancer is unclear. This study aimed to investigate the role of PQ on ROS accumulation and mitochondrial dysfunction in H-ras mutated HepG2 (HepG2PQ ethanol extract-induced HepG2PQ treatment affected cell migration and colony formation in HepG2Taken together these results provide a new functional significance for the role of PQ in treating HepG2

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.

Symptoms of Parkinson’s disease (PD) caused by loss of dopaminergic neurons are accompanied by movement disorders, including tremors, rigidity, bradykinesia, and akinesia. Non-human primate (NHP) models with PD play an essential role in the analysis of PD pathophysiology and behavior symptoms. As impairments of hand dexterity function can affect activities of daily living in patients with PD, research on hand dexterity function in NHP models with chronic PD is essential. Traditional rating scales previously used in the evaluation of animal spontaneous behavior were insufficient due to factors related to subjectivity and passivity. Thus, experimentally designed applications for an appropriate apparatus are necessary. In this study, we aimed to longitudinally assess hand dexterity function using hand dexterity task (HDT) in NHP-PD models. To validate this assessment, we analyzed an alteration in Parkinsonian tremor symptoms, loss of dopaminergic neuron, and positron emission tomography (PET) imaging of dopamine transporters (DAT) in these models. HDT latency significantly increased in NHP-PD models. In addition, a significant inverse correlation between HDT and DAT was identified, but no local bias was found. The correlation with intention tremor symptoms was lower than the resting tremor. In conclusion, the evaluation of HDT may reflect behavioral symptoms of NHP-PD models. Furthermore, HDT was effectively used to experimentally distinguish intention tremors from other tremors.

A long-term change of a subtidal macroalgal assemblage has been investigated in Maxwell Bay, King George Island (KGI) of the Antarctic coast by a revisit survey after 30 years. Field surveys were done by SCUBA diving at six sites in 2016–2018 to directly compare with the previous survey conducted in 1988–1993 at the same sites. The total number of macroalgal species was similar between the previous and the present survey, 25 and 27 species respectively. However, the macroalgal assemblage changed substantially with the average similarity of 48.2% between the two surveys. Also, the species-level abundance showed a high variability between surveys. On the other hand, over the 30 years interval there was little overall change at the between-site level hierarchical structure in the subtidal communities of Maxwell Bay. The sites near the penguin rookery consistently showed the highest biodiversity, indicating the importance of land-based nutrients input in Antarctic coastal habitats. A noticeable pattern change over 30 years was the increase of Desmarestia complex and Plocamium cartilagineum and the decrease of Himantothallus grandifolius. Both groups are still dominant, but the shift from Himantothallus to Desmarestia-Plocamium may reflects temperature rise on the Maxwell Bay coast compared to the past.

Objective Evaluation of sensitivity and specificity of CT and fluorodeoxyglucose-positron emission tomography for pre-surgical staging of mediastinal lymph node metastases (N2/N3) of non-small-cell-lung-cancers ≤30 mm. Methods We reviewed a total of 263 patients from a prospective cohort study, who underwent resection including mediastinal lymph nodes, for first primary non-small-cell-lung-cancer ≤30 mm in maximum diameter on pre-surgical CT. Cutoff criteria for short-axis diameter on CT of the largest N2/N3 node of 10, 15, and 20 mm and positron emission uptake of 2.5, 3.0, and 4.0 were evaluated using Area-Under-the-Curve (AUC) assessment. Accuracy criterion was used to determine the optimal cutoffs. Results Of 263 patients, 9 had nonsolid, 42 part-solid, and 212 solid non-small-cell-lung-cancers. Post-surgically, none of the 51 patients with nonsolid or part-solid cancers had mediastinal lymph node metastases. Among the 212 patients with solid cancers, 23 had N2 node metastases. For the 212 patients with solid cancers, the AUC for CT lymph node measurements was 0.67 (95% CI: 0.57-0.77), significantly higher (p = 0.001) than chance alone, while the AUC for SUVmax measurements, 0.56 (95% CI: 0.48-0.65), was not (p = 0.13). Optimal CT cutoff was >20 mm had low sensitivity of 30.4% (95% CI: 11.6%-49.2%) but high specificity of 99.5% (95% CI: 98.4%-100.0%). Conclusion Based on these results, clinical Stage IA for non-small-cell-lung-cancers with nonsolid, part-solid, or solid consistency should be based on pre-surgical CT maximum tumor diameter and lymph node short-axis measurements on CT ≤20 mm. Further prospective evaluation of these clinical Stage IA staging criteria is needed.

Excessive microglial cell activation in the brain can lead to the production of various neurotoxic factors (e.g., pro-inflammatory cytokines, nitric oxide) which can, in turn, initiate neurodegenerative processes. Recent research has been reported that mitochondrial dynamics regulate the inflammatory response of lipopolysaccharide (LPS). Isoliquiritigenin (ISL) is a compound found in Glycyrrhizae radix with anti-inflammatory and antioxidant properties. In this study, we investigated the function of ISL on the LPS-induced pro-inflammatory response in BV-2 microglial cells. We showed that ISL reduced the LPS-induced increase in pro-inflammatory mediators (e.g., nitric oxide and pro-inflammatory cytokines) via the inhibition of ERK/p38/NF-κB activation and the generation of reactive oxygen species (ROS). Furthermore, ISL inhibited the excessive mitochondrial fission induced by LPS, regulating mitochondrial ROS generation and pro-inflammatory response by suppressing the calcium/calcineurin pathway to dephosphorylate Drp1 at the serine 637 residue. Interestingly, the ISL pretreatment reduced the number of apoptotic cells and levels of cleaved caspase3/PARP, compared to LPS-treated cells. Our findings suggested that ISL ameliorated the pro-inflammatory response of microglia by inhibiting dephosphorylation of Drp1 (Ser637)-dependent mitochondrial fission. This study provides the first evidence for the effects of ISL against LPS-induced inflammatory response related and its link to mitochondrial fission and the calcium/calcineurin pathway. Consequently, we also identified the protective effects of ISL against LPS-induced microglial apoptosis, highlighting the pharmacological role of ISL in microglial inflammation-mediated neurodegeneration.

Blood pressure (BP) is a vital sign that provides fundamental health information regarding patients. Continuous BP monitoring is important for patients with hypertension. Various studies have proposed cuff-less BP monitoring methods using pulse transit time. We propose an end-to-end deep learning architecture using only raw signals without the process of extracting features to improve the BP estimation performance using the attention mechanism. The proposed model consisted of a convolutional neural network, a bidirectional gated recurrent unit, and an attention mechanism. The model was trained by a calibration-based method, using the data of each subject. The performance of the model was compared to the model that used each combination of the three signals, and the model with the attention mechanism showed better performance than other state-of-the-art methods, including conventional linear regression method using pulse transit time (PTT). A total of 15 subjects were recruited, and electrocardiogram, ballistocardiogram, and photoplethysmogram levels were measured. The 95% confidence interval of the reference BP was [86.34, 143.74] and [51.28, 88.74] for systolic BP (SBP) and diastolic BP (DBP), respectively. The R 2 values were 0.52 and 0.49, and the mean-absolute-error values were 4.06 &plusmn, 4.04 and 3.33 &plusmn, 3.42 for SBP and DBP, respectively. In addition, the results complied with global standards. The results show the applicability of the proposed model as an analytical metric for BP estimation.

Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence.

s Background Lymph node (LN) metastasis is negligible in early gastric cancer (EGC) within expanded criteria for endoscopic submucosal dissection (ESD). However, regional lymph nodes in abdominal CT scans are sometimes enlarged in patients with EGC within the expanded criteria for endoscopic submucosal dissection (ESD). In this study, we investigated the clinical significance of regional lymph node enlargement on abdominal CT scan in patients with EGC within the expanded criteria for ESD. Methods From December 2010 to April 2015, among 301 patients with EGC within the ESD expanded criteria, 47 patients with regional lymph node enlargement shown by abdominal CT scan were prospectively enrolled. We performed surgical resection or periodic follow-up with abdominal CT scans and upper endoscopy every 6 months to evaluate whether the enlarged lymph nodes are due to metastasis or a reactive change. Results The mean age of the 47 patients (38 males, 9 female) was 64.8 years. The enlarged lymph nodes were usually single (26/47, 44.6%) and sized as follows: 11 nodes were ≤ 5 mm, 19 were 6–10 mm, and 17 were ≥ 10 mm. Four of the 47 patients initially underwent surgical resection, and 8 patients underwent surgical resection after ESD. However, there was no lymph node metastasis in surgical specimens. Thirty-five patients received ESD and periodically followed up at a median duration of 56 months (IQR: 44–59 month). The enlarged lymph node disappeared in 12 of 35 patients, decreased in 9 patients and remained the same size in 13 patients, and increased in 1 patient. Conclusion Regional lymph node enlargement on abdominal CT scan in patients within expanded criteria for ESD of ECG may be not due to metastasis but a reactive change.

The CRISPR-Cas9 system is widely used for target-specific genome engineering. Cpf1 is one of the CRISPR effectors that controls target genes by recognizing thymine-rich protospacer adjacent motif (PAM) sequences. Cpf1 has a higher sensitivity to mismatches in the guide RNA than does Cas9; therefore, off-target sequence recognition and cleavage are lower. However, it tolerates mismatches in regions distant from the PAM sequence (TTTN or TTN) in the protospacer, and off-target cleavage issues may become more problematic when Cpf1 activity is improved for therapeutic purposes. In our study, we investigated off-target cleavage by Cpf1 and modified the Cpf1 (cr)RNA to address the off-target cleavage issue. We developed a CRISPR-Cpf1 that can induce mutations in target DNA sequences in a highly specific and effective manner by partially substituting the (cr)RNA with DNA to change the energy potential of base pairing to the target DNA. A model to explain how chimeric (cr)RNA guided CRISPR-Cpf1 and SpCas9 nickase effectively work in the intracellular genome is suggested. In our results, CRISPR-Cpf1 induces less off-target mutations at the cell level, when chimeric DNA-RNA guide was used for genome editing. This study has a potential for therapeutic applications in incurable diseases caused by genetic mutation.

Background/Aim: Dermal mesenchymal stem cells (DMSCs) are pluripotent stem cells found in the skin which maintain the thickness of the dermal layer and participate in skin wound healing. Materials and Methods: The MTT assay was performed to detect cell proliferation and cell-cycle progression and cell-surface markers were assessed by flow cytometry. The levels of proteins in related signaling pathways were detected by western blotting assay and the translocation of β-catenin into the nucleus were detected by immunofluorescence. Red oil O staining was performed to examine the differentiational ability of DMSCs. Results: Knockout of PRDX2 inhibited DMSC cell growth, and cell-cycle arrest at G(0)/G(1 )phase; p16, p21 and cyclin D1 expression levels in Prdx2 knockout DMSCs were significantly increased. Furthermore, AKT phosphorylation were significantly increased in Prdx2 knockout DMSCs, GSK3β activity were inhibited, result in β-Catenin accumulated in the nucleus. Conclusion: In conclusion, these results demonstrated that PRDX2 plays a pivotal role in regulating the proliferation of DMSCs, and this is closely related to the AKT/glycogen synthase kinase 3 beta/β-catenin signaling pathway.

The thermal environment experienced by human is significantly affected by the radiant heat. Information regarding the effect of radiant temperature on the occupants in a building is necessary for a comprehensive evaluation of indoor thermal comfort and for a corresponding control of the building's passive and active systems. This paper presents a real-time estimation method of MRT distributions in indoor spaces that does not require a direct installation of measurement devices at occupant locations. To consider the effect of longwave radiation, a pan-tilt IR camera was applied to remotely measure interior surface temperatures. For shortwave radiation, a single pyranometer installed outside was applied to estimate diffuse and direct irradiance at the occupant locations. The real-time MRT monitoring process and the Pan-tilt IR scanning system⁺ are derived. An experiment was performed to validate the applicability of the derived MRT monitoring process. The MRT at three target locations were measured by a globe thermometer and also estimated by the derived method. The measured and estimated MRT values were compared, and the results showed high goodness of fits as the R2 values were higher than 0.80 for all target locations. The monitoring results confirm that the MRT value can differ up to 15 °C according to occupant locations because of solar radiation. This paper discusses the applicability in various fields and possible future works of the proposed MRT estimation process.

In this study, we analysed the ahpD gene from Corynebacterium glutamicum, which may function in a H2O2-mediated stress responses. Cells overexpressing C. glutamicum ahpD (P180-ahpD) showed increased sensitivity to H2O2 when exposed to the latter in concentrations of 8 mM or greater while showing reduced expression of katA, which encodes catalase. On the other hand, cells that lack ahpD (ΔahpD) displayed increased sensitivity when exposed to low levels of H2O2 while showing katA transcription that was comparable to the level in the wild-type strain. Accordingly, transcription of ahpD and katA was stimulated by low and high concentration of H2O2, respectively. Further, the NAD+/NADH ratio was severely reduced in the ΔahpD (3.03) and P180-ahpD (0.47) strains as compared with that in the wild-type (4.55) strain. Transcriptional analysis indicated that ahpD and upstream genes such as cg2675, cg2676, cg2677 and cg2678, which were annotated as ABC-type transporter, were organized into an operon. Collectively, these findings indicate that C. glutamicum possesses bi-level defence pathways against hydrogen peroxide, involving katA and ahpD. Further, ahpD, along with cg2675-cg2678 genes, may play a novel role in cellular activities against oxidative stress.

This paper describes an experimental investigation of the low-cycle fatigue (LCF) behavior of welded flange-bolted web (WFBW) connections, which are commonly employed in high-rise steel moment-resisting frames (MRFs) in Japan. The main parameters investigated in this study were (1) bolt configuration of the web connection and (2) steel grade. According to test results, LCF capacity depends on the slip behavior of different bolt configurations, even at relatively minor inelastic rotations. Slip behavior effects can be evaluated by the yield strength of the shear plate or the slip-critical strength; for specimens whose shear plate yield strength was designed to be higher than the slip-critical strength, LCF capacity showed that the upper limit can neglect slip behavior. Furthermore, it was shown that LCF behavior can be evaluated by the same fatigue curve in the relationship of fatigue capacity and beam rotation amplitude, regardless of steel yield stress.

Numerous studies suggest that glutamate toxicity is a major contributor to neuronal dysfunction and death in several neurodegenerative diseases. In our previous study, isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis showed neuroprotective effects against neuronal cell death mediated by intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential. However, the mechanisms by which ISL protects against glutamate-induced oxidative stress are unknown. In the present study, we focused on the cellular and molecular mechanisms underlying the inhibition of ROS production and induction of mitochondrial dysfunction by ISL in glutamate-stimulated HT22 mouse hippocampal neuron cells. The results revealed that ISL inhibited glutamate-induced mitochondrial ROS production and decline of glutathione levels and ATP generation in HT22 cells. Interestingly, we discovered that ISL prevents glutamate-induced mitochondrial fission by inhibiting the dephosphorylation of Drp1 at the serine 637 residue, which is a regulatory factor of mitochondrial dynamics, and both a S637D mutation of Drp1, which resulted in a phosphorylation-mimetic form of Drp1 at Ser637, and mitochondria-targeted antioxidant Mito-TEMPO inhibited glutamate-induced mitochondrial fission. Furthermore, ISL also prevented the increase of intracellular calcium accompanied by activation of calcineurin, which is a key regulator of dephosphorylation of Drp1 (Ser637), in glutamate-treated HT22 cells. Taken together, our results demonstrated that ISL protects against glutamate-induced mitochondrial fission by inhibiting the increase of mitochondrial ROS and intracellular calcium, which are accompanied by dephosphorylation of Drp1 (Ser637), and consequently attenuates glutamate-induced neuronal cell death. Therefore, these findings suggest that ISL exhibits the potential for protection against glutamate toxicity. These results may contribute to the development of new drugs and novel strategies for the treatment of neurodegenerative disorders related to glutamate toxicity.

In various neuronal diseases, the activation of microglia contributes to the production of excessive neurotoxic factors, such as pro-inflammatory mediators. In particular, the overproduction of pro-inflammatory cytokines and nitric oxide (NO) has critical effects on the development of neurodegenerative diseases and gliomas in the brain. Recent studies have suggested that isocitrate dehydrogenase 2 (IDH2) plays a key role in inducing gliomas and neurodegeneration. IDH2 dysfunction has been linked to various cancers and neurodegenerative diseases associated with uncontrolled inflammatory responses, such as the excessive generation of pro-inflammatory cytokines. In this study, we demonstrate that IDH2 contributes to the regulation of pro-inflammatory mediators in microglia. The downregulation of IDH2 decreased the lipopolysaccharide (LPS)-induced pro-inflammatory response in BV-2 and primary microglial cells. Furthermore, IDH2 deficiency downregulated pro-inflammatory mediators via modulation of the ERK and NF-κB pathways. These results indicate that IDH2 is a potential target for the regulation of pro-inflammatory responses in LPS-activated microglial cells. Our findings also provide a basis for the development of new therapies for pro-inflammatory responses in dysfunction-associated neuronal diseases.