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Epidemiological studies have linked fine dust pollution to depression, yet the underlying mechanisms remain unclear. Oxidative stress and endoplasmic reticulum (ER) stress are known contributors to depression, but their induction by particulate matter (PM), particularly PM2.5, in animal models has been limited. This study aimed to establish a rat model of PM2.5-induced depression-like behaviors and elucidate the underlying molecular mechanisms. Adult male Sprague–Dawley rats received daily intranasal PM2.5 for four weeks. Behavioral assessments, including the open field test (OFT), forced swim test (FST), and light-dark box (LDB) test, were conducted weekly. PM2.5-exposed rats displayed depressive-like behaviors, particularly in the FST, reflecting decreased motivation and learned helplessness. Molecular analyses indicated a specific increase in ER stress markers (CHOP, eIF2α, GRP78, and P16) and NOX4 in the hypothalamus, while other brain regions (striatum, cortex, and hippocampus) were not as pronounced. Additionally, PM2.5 exposure reduced tyrosine hydroxylase (TH) levels in the hypothalamus, suggesting impaired dopamine synthesis. These findings indicate that PM2.5 induces depressive-like behaviors via hypothalamic ER stress and oxidative stress pathways, leading to dopaminergic dysfunction. Targeting oxidative and ER stress within the hypothalamus may offer new therapeutic strategies for treating depression associated with environmental pollutants. [ABSTRACT FROM AUTHOR]

Background: The Antarctic environment is susceptible to the introduction of non-native species due to its unique ecosystem, which has evolved under geographical isolation and extreme climatic conditions over an extended period. The recent introduction of the non-native winter crane fly, Trichocera maculipennis, to maritime Antarctica may pose a potential threat to the Antarctic ecosystem. In this study, we evaluated the possibility of the mechanical transmission of viruses by T. maculipennis. Methods: We assessed the potential for the mechanical transmission of viruses using next-generation sequencing (NGS), quantitative PCR (qPCR), and virus isolation methods from T. maculipennis (Tm)-related samples (Tm body-wash fluid and Tm body-ground samples) collected from habitats and sewage treatment facilities located at three research stations in Antarctica. Results: Virome analysis detected the genomic fragments of human adenovirus (AdV) and human endogenous retrovirus (HERV) in Tm-related samples. These viruses are commonly found in human feces. In addition, plant viruses, such as pepper mild mottle virus (PMMoV) and cucumber green mottle mosaic virus (CGMMV), both known indicators of enteric viruses, were identified in all Tm-related samples, likely originating from wastewater. However, the low quantities of AdV and HERV genomes detected in Tm-related samples through qPCR, coupled with the non-viability of AdV in virus isolation tests, indicate that T. maculipennis has limited potential for mechanical transmission under the conditions in the studies. Conclusions: Our study represents the first evaluation of the potential risk of non-native species serving as vectors for viral pathogens in Antarctica. Although the viruses detected were in relatively low quantities and non-viable, this study highlights the importance of further evaluating the risks associated with non-native species, particularly as the likelihood of their introduction increases to Antarctica due to climate change and increased human activity. [ABSTRACT FROM AUTHOR]

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

With increasing interest in the inflammation-pathogen infection hypothesis and its potential links to Alzheimer's disease (AD) development, there is growing consideration of using upper respiratory infection (URI) treatments as interventions for AD. This nested case–control study explored the potential association between prior URI histories and AD development in a Korean adult population using the national health screening cohort data (2002–2019). The study included 26,920 AD patients and 107,680 matched control individuals, focusing on those seeking respiratory treatment. Logistic regression analyses assessed the impact of URI histories and treatment on AD risk while adjusting for covariates. Our results revealed that over a 1-year period, individuals with URI histories (≥1, ≥2, or ≥3 instances) exhibited decreasing probabilities of developing AD, with risk reductions of 19%, 15%, and 12%, respectively. Expanding our investigation to a 2-year period consistently showed a 17% reduction in AD risk. This effect remained robust across diverse demographic groups and after adjusting for covariates, encompassing comorbidities, hypertension, hyperlipidemia, blood glucose levels, and lifestyle factors. Subgroup analyses further substantiated this association. In conclusion, our findings cautiously suggest a potential protective role of prior URI treatment histories in mitigating the risk of AD development. [ABSTRACT FROM AUTHOR]

Despite the growing prevalence of gout and its associated health concerns as a chronic disorder, population-based studies on its link to migraines are scarce. We conducted a 16-year longitudinal study in a Korean population to investigate the relationship between gout and migraines, including different subtypes. We enrolled 23,137 patients with gout and matched them with 92,548 controls based on age, sex, income, and residence. Using Cox proportional hazards models, we calculated hazard ratios to assess the likelihood of migraines while considering relevant factors. During the follow-up, 1000 gout patients and 3214 controls experienced migraines. After adjusting for various factors, including demographics, health-related variables, and weight categories, the gout group had a 1.26-fold higher likelihood of developing migraines compared to the group without gout. This association was particularly strong for migraines without aura, while it was not significant for migraines with aura. In summary, our study reveals a significant link between gout and migraines in the Korean population, emphasizing the complex relationship among chronic disorders, with a specific focus on migraine subtypes. [ABSTRACT FROM AUTHOR]

In the quest to combat infections attributable to antibiotic-resistant superbacteria, an essential oil derived from the needles of Pinus koraiensis Sieb. et Zucc. (PKEO) has emerged as a promising solution. In this study, we demonstrate that PKEO can be used to inhibit the growth, glucose metabolite acidogenicity, and biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA). Quantitative PCR analysis provided direct evidence that PKEO reduces the mRNA expression of the accessory gene regulator A (agrA) and staphylococcal accessory regulator A (sarA), thereby indicating its inhibitory effect on pathogenic regulatory genes. Chromatographic analyses of PKEO identified terpene hydrocarbons as prominent essential oil constituents. These compounds, notably α-pinene, limonene, and β-caryophyllene, have been established to have antimicrobial properties. Our findings indicate that an oil derived from P. koraiensis can effectively combat antibiotic-resistant strains by disrupting the pathogenicity regulatory system, thereby establishing PKEO as a promising candidate for the treatment of MRSA infections. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the potential link between Alzheimer's disease (AD) and the probability of developing various cancers using a large cohort dataset in Korea from matching 24,664 Korean citizens with AD and without a history of cancer with 98,656 non-AD and noncancer Korean citizens. The results revealed that patients with AD had a significantly lower likelihood of developing overall malignancy as well as specific types of cancer compared to the control group. Notably, pancreatic cancer showed the strongest inverse relationship with AD. The protective effect against certain organ-specific cancers persisted throughout the 16-year follow-up period, particularly in individuals aged 60 years and above. These findings suggest that Korean patients with AD may have a decreased risk of malignancy, highlighting the need to explore the connection between AD and cancer risk. The link between Alzheimer's disease and cancer risk is a concern in public health. However, research has yielded limited and sometimes contrasting results, suggesting the need for more validation. We analyzed a large cohort to examine the long-term association between Alzheimer's disease (AD) and the risk of developing cancer. In total, 24,664 AD patients and 98,656 control participants were selected from the National Health Insurance Cohort database of Korea, spanning from 2002 to 2019. Propensity score matching and overlap-weighted adjustment techniques were used to balance the standardized differences between the AD and control groups. The Cox proportional hazards model was applied to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for various cancers, considering relevant covariates. Results indicated that patients with AD had a significantly lower likelihood of overall malignancy (HR 0.63; 95% CI, 0.59–0.68) and each of the 10 site-specific cancers compared to the control group. Among these, pancreatic cancer (HR, 0.50) exhibited the strongest inverse association, followed by hepatic (HR, 0.60), gastric (HR, 0.63), kidney (HR, 0.63), lung (HR, 0.64), thyroid (HR, 0.65), colorectal (HR, 0.67), gallbladder and biliary duct (HR, 0.73), hematologic malignancy (HR, 0.73), and bladder cancers (HR, 0.76). This protective effect against certain organ-specific cancers persisted over the 16-year follow-up period, except for in kidney cancer and hematologic malignancies. The protective effect against specific cancer types (gastric, colorectal, lung, hepatic, and pancreatic) was more prominent in individuals aged 60 years and older, regardless of their sex. However, there were some variations in the specific types of cancer observed between males and females. In summary, Korean patients with AD had a lower risk of cancer, especially in individuals 60 years and older, during the 16-year follow-up period. [ABSTRACT FROM AUTHOR]

Background: Identifying the risk factors for falls among the elderly population is arguably one of the most imperative public health issues in the current aging society. Objectives: This study aimed to determine the associations between depressive symptoms, subjective cognitive decline (SCD), and poor subjective sleep quality and the risk of slips/falls in a Korean older population. Methods: This cross-sectional study involved 228,340 elderly individuals living in Korea. Measurements included self-reported depressive symptoms, SCD, and self-reported sleep quality. The risk of slips/falls was dichotomized depending on whether slips/falls had occurred during the past year, and the associations between different risk factors and slips/falls were explored. Multiple logistic regression was used to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Complex sampling methods were used to estimate the weighted value of each participant. Results: The risk of slips/falls was significantly associated with high levels of depressive symptoms (adjusted OR 1.06, 95% CI: 1.05–1.07) and SCD (adjusted OR 1.33, 95% CI: 1.19–1.50). Regarding each sleep quality component, the adjusted ORs for slips/falls were 1.85 for very poor sleep quality, 1.49 for long sleep latency, 1.04 for <5 h of sleep duration, 1.32 for low sleep efficiency, 2.78 for high sleep disturbance, 1.52 for the use of sleep medication ≥3 times a week, and 1.82 for high daytime dysfunction due to sleep problems compared to the respective good sleep conditions. Conclusions: Our results demonstrated that depressive symptoms, SCD, and poor subjective sleep quality are independent factors affecting the occurrence of slips/falls. Thus, efforts to manage depressive symptoms and cognitive decline early and to improve sleep quality can be an alternative strategy to decrease the likelihood of falls. [ABSTRACT FROM AUTHOR]

Singlet fission, a rapid exciton doubling process via inverse Auger recombination, is recognized as one of the most practical and feasible means for overcoming the Shockley–Queisser limit. Singlet fission solar cells are generally developed by integrating photon downconversion organic semiconductors into conventional photovoltaic devices to break the maximum photovoltaic response of the host semiconductors by virtue of extra triplet excitons. In this regard, proper matching of two different semiconductors and heterointerface engineering are both crucial for highly efficient singlet fission solar cells. Therefore, the aim of this study is to review the prerequisite conditions for efficient triplet transfer at the heterointerfaces and thus highlight the robust spin and valley degrees of freedom of transition metal dichalcogenides with the ultimate goal of stimulating research into next‐generation singlet fission solar cells. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate whether pretreatment kinetic features from ultrafast DCE-MRI are associated with pathological complete response (pCR) in patients with invasive breast cancer and according to immunohistochemistry (IHC) subtype. Methods: Between August 2018 and June 2019, 256 consecutive breast cancer patients (mean age, 50.2 years; range, 25–86 years) who underwent both ultrafast and conventional DCE-MRI and surgery following neoadjuvant chemotherapy were included. DCE-MRI kinetic features were obtained from pretreatment MRI data. Time-to-enhancement, maximal slope (MS), and volumes at U1 and U2 (U1, time point at which the lesion starts to enhance; U2, subsequent time point after U1) were derived from ultrafast MRI. Logistic regression analysis was performed to identify factors associated with pCR. Results: Overall, 41.4% of all patients achieved pCR. None of the kinetic features was associated with pCR when including all cancers. Among ultrafast DCE-MRI kinetic features, a lower MS (OR, 0.982; p = 0.040) was associated with pCR at univariable analysis in hormone receptor (HR)–positive cancers. In triple-negative cancers, a higher volume ratio U1/U2 was associated with pCR at univariable (OR, 11.787; p = 0.006) and multivariable analysis (OR, 14.811; p = 0.005). Among conventional DCE-MRI kinetic features, a lower peak enhancement (OR, 0.993; p = 0.031) and a lower percentage of washout (OR, 0.904; p = 0.039) was associated with pCR only in HR-positive cancers at univariable analysis. Conclusions: A higher volume ratio of U1/U2 derived from ultrafast DCE-MRI was independently associated with pCR in triple-negative invasive breast cancer. Key Points: • The ratio of tumor volumes obtained at the first (U1) and second time points (U2) of enhancement was independently associated with pCR in triple-negative invasive breast cancers. • Ultrafast MRI has the potential to improve accuracy in predicting treatment response and personalizing therapy. [ABSTRACT FROM AUTHOR]

Background: Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory disease in humans, with a case fatality rate of approximately 35%, thus posing a considerable threat to public health. The lack of approved vaccines or antivirals currently constitutes a barrier in controlling disease outbreaks and spread. Methods: In this study, using a mammalian expression system, which is advantageous for maintaining correct protein glycosylation patterns, we constructed chimeric MERS-CoV virus-like particles (VLPs) and determined their immunogenicity and protective efficacy in mice. Results: Western blot and cryo-electron microscopy analyses demonstrated that MERS-CoV VLPs were efficiently produced in cells co-transfected with MERS-CoV spike (S), envelope, membrane and murine hepatitis virus nucleocapsid genes. We examined their ability as a vaccine in a human dipeptidyl peptidase 4 knock-in C57BL/6 congenic mouse model. Mice immunized with MERS VLPs produced S-specific antibodies with virus neutralization activity. Furthermore, MERS-CoV VLP immunization provided complete protection against a lethal challenge with mouse-adapted MERS-CoV and improved virus clearance in the lung. Conclusions: Overall, these data demonstrate that MERS-CoV VLPs have excellent immunogenicity and represent a promising vaccine candidate. [ABSTRACT FROM AUTHOR]

Radiation-induced skin injury (RISI) is a main side effect of radiotherapy for cancer patients, with vascular damage being a common pathogenesis of acute and chronic RISI. Despite the severity of RISI, there are few treatments for it that are in clinical use. 2-Methoxyestradiol (2-ME) has been reported to regulate the radiation-induced vascular endothelial-to-mesenchymal transition. Thus, we investigated 2-ME as a potent anti-cancer and hypoxia-inducible factor 1 alpha (HIF-1α) inhibitor drug that prevents RISI by targeting HIF-1α. 2-ME treatment prior to and post irradiation inhibited RISI on the skin of C57/BL6 mice. 2-ME also reduced radiation-induced inflammation, skin thickness, and vascular fibrosis. In particular, post-treatment with 2-ME after irradiation repaired the damaged vessels on the irradiated dermal skin, inhibiting endothelial HIF-1α expression. In addition to the increase in vascular density, post-treatment with 2-ME showed fibrotic changes in residual vessels with SMA+CD31+ on the irradiated skin. Furthermore, 2-ME significantly inhibited fibrotic changes and accumulated DNA damage in irradiated human dermal microvascular endothelial cells. Therefore, we suggest that 2-ME may be a potent therapeutic agent for RISI. [ABSTRACT FROM AUTHOR]

Introduction: Findings on the association between statin therapy and Parkinson's disease (PD) occurrence have been inconsistent. This study aimed to identify the association between statin use and PD in participants with a history of hyperlipidemia or blood cholesterol >200 in a Korean population to exclude nonstatin users owing to normal lipid values.Methods: We conducted a nested case-control analysis using the Korean National Health Insurance Service-National Sample Cohort assessed between 2002 and 2015. We identified 3026 PD cases. A total of 12,104 controls were then individually matched by age, sex, income, and region of residence at a ratio of 1:4. Potential confounders comprised basic demographic factors, lifestyle factors, various medical conditions and comorbidities. A conditional/unconditional logistic regression method was applied.Results: Compared with statin use for <6 months, adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for 6-12 months of statin use and ≥12 months of statin use were 1.03 (0.92-1.15) and 1.61 (1.35-1.93) after adjustment for confounders, respectively (P = 0.664 and P < 0.001). In analyses according to statin solubility, only the association between lipophilic statin use for ≥12 months and PD maintained statistical significance, with an aOR of 1.64 (95% CI = 1.34-2.01, P < 0.001). These relations were consistent in subgroup analyses by covariates.Conclusions: Statin use for more than 12 months was associated with a higher probability of PD in the Korean population with hyperlipidemia. This probability was significant for lipophilic statins but not hydrophilic statins. [ABSTRACT FROM AUTHOR]

Few studies have shown an increased risk of Parkinson's disease (PD) with the use of proton pump inhibitors (PPIs), and the pathophysiological mechanism for this association has not been unveiled. This study examined the relationship between PPI use and PD in a Korean population. We investigated 3026 PD patients and 12,104 controls who were matched by age, sex, income, and region of residence at a ratio of 1:4 in the Korean National Health Insurance Service, National Sample Cohort between 2002 and 2015. We estimated the associations between current and past use of PPIs and PD using odds ratios (ORs) and 95% confidence intervals (CIs) in a conditional/unconditional logistic regression after adjusting for probable confounders. Compared with PPI nonusers, both current users and past users had significantly greater odds of having PD, with ORs of 1.63 (95% CI = 1.44–1.84) and 1.12 (95% CI = 1.01–1.25), respectively. A significant association with PD was observed in individuals who used PPIs for 30–90 days and ≥90 days (OR = 1.26 and 1.64, 95% CI = 1.12–1.43 and 1.43–1.89) but not among those who used PPIs for <30 days. Both current and past use of PPIs associated with a higher probability of PD in the Korean population. Our study provides evidence regarding the association between PPI exposure and PD, but further investigation and possible explanations are warranted. [ABSTRACT FROM AUTHOR]

The incidence of severe inflammatory diseases caused by chronic inflammation has increased owing to unprecedented changes brought about by industrialization. In this study, we aimed to assess the effect of treatment of lipopolysaccharide- (LPS-) induced murine macrophages with Commelina communis Linne extract (CCE) on synthesis of nitric oxide (NO), hypersecretion of proinflammatory cytokines, intranuclear transition of the p65 subunit of nuclear factor- (NF-) κB, and degradation of the NF-κB inhibitor IκBα. Notably, CCE treatment did not affect cell viability even at a final concentration of 1.5 mg/mL. At a high concentration of CCE, the LPS-induced high levels of NO, tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6 were decreased via downregulation of inducible NO synthase and proinflammatory cytokine mRNA expression. Furthermore, phosphorylation of IκBα was significantly decreased upon CCE treatment, and the intranuclear transition of NF-κB p65 triggered by LPS was inhibited at a high concentration of CCE. Polyphenols and flavonoids, secondary metabolites in CCE that regulate the NF-κB pathway, may be responsible for its anti-inflammatory activity. We suggest that CCE has anti-inflammatory effects related to suppression of the NF-κB pathway and can be used to treat chronic inflammation. [ABSTRACT FROM AUTHOR]

Pyroptosis is a form of programmed cell death characterized by gasdermin (GSDM)-mediated pore formation in the cell membrane, resulting in the release of pro-inflammatory cytokines and cellular lysis. Increasing evidence has shown that pyroptosis is responsible for the progression of various pulmonary disorders. The inhalation of polyhexamethylene guanidine (PHMG) causes severe lung inflammation and pulmonary toxicity; however, the underlying mechanisms are unknown. Therefore, in this study, we investigate the role of pyroptosis in PHMG-induced pulmonary toxicity. We exposed bronchial epithelial cells, BEAS-2B, to PHMG phosphate (PHMG-p) and evaluated cell death type, reactive oxygen species (ROS) levels, and relative expression levels of pyroptosis-related proteins. Our data revealed that PHMG-p reduced viability and induced morphological alterations in BEAS-2B cells. Exposure to PHMG-p induced excessive accumulation of mitochondrial ROS (mtROS) in BEAS-2B cells. PHMG-p activated caspase-dependent apoptosis as well as NLRP3/caspase-1/GSDMD-mediated- and caspase-3/GSDME-mediated pyroptosis through mitochondrial oxidative stress in BEAS-2B cells. Notably, PHMG-p reduced mitochondrial respiratory function and induced the translocation of Bax and cleaved GSDM into the mitochondria, leading to mitochondrial dysfunction. Our results enhanced our understanding of PHMG-p-induced lung toxicity by demonstrating that PHMG-p induces pyroptosis via mtROS-induced mitochondrial dysfunction in bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

The interest in skin microbiome differences by ethnicity, age, and gender is increasing. Compared to other ethnic groups, studies on the skin microbiome of Koreans remains insufficient; we investigated facial skin microbiome characteristics according to gender and age among Koreans. Fifty-one healthy participants were recruited, the facial skin characteristics of each donor were investigated, their skin bacterial DNA was isolated and metagenomic analysis was performed. The donors were divided into two groups for age and sex each to analyze their skin microbiomes. Moreover, we investigated the correlation between the skin microbiome and clinical characteristics. The alpha diversity of the skin microbiome was significantly higher in the elderly, and beta diversity was significantly different according to age. The comparative skin microbials showed that the genus Lawsonella was more abundant in the younger age group, and Enhydrobacter was predominant in the older age group. Staphylococcus and Corynebacterium were more abundant in males, while Lactobacillus was more abundant in females. Lawsonella had a negative correlation with skin moisture and brown spots. Staphylococcus and Corynebacterium both had negative correlations with the number of UV spots and positive correlations with transepidermal water loss (TEWL). Furthermore, Staphylococcus aureus had a negative correlation with skin moisture parameters. [ABSTRACT FROM AUTHOR]

Objectives: Little is known concerning whether subjective cognitive decline (SCD) is associated with sleep quality. This study aimed to identify the association between self-reported quality of sleep and SCD in a large population of middle-aged and older adults in Korea.Methods: We conducted this study based on data collected from the 2018 Korean Community Health Survey. Individuals aged 40 years and older who responded to the Behavioral Risk Factor Surveillance System (BRFSS) and Pittsburgh Sleep Quality Index (PSQI) assessments and did not lack data about multiple covariates were included. A total of 37,712 respondents with SCD and 135,119 those without SCD were included. Sleep quality was estimated using the PSQI, which includes seven self-reported components for sleep health assessment. SCD was assessed using the BRFSS. Logistic regression models adjusted for confounders were used to examine whether each component of the sleep quality index was related to SCD. Additional analysis of the correlation between quantified scores for each component and SCD-related functional limitations as ordinal variables was performed.Results: The mean age was 62.7 years in the SCD group and 56.4 years in the control group. In total, 13,777 (28.9%) respondents were male in the SCD group and 62,439 (50.7%) in the control group. The adjusted odds ratios of SCD were 1.25 for very bad sleep quality, 1.26 for long sleep latency, 1.16 for <5 h of sleep duration, 1.08 for <65% habitual sleep efficiency, 2.29 for high sleep disturbance, 1.26 for use of sleep medication ≥3 times a week, and 2.47 for high daytime dysfunction due to sleep problems compared to good sleep conditions. Furthermore, a higher score for each component of the sleep quality index correlated with greater SCD-related functional limitations.Conclusions: Our study provides evidence that poor sleep quality is closely related to both SCD and SCD-related functional limitations. [ABSTRACT FROM AUTHOR]

αKlotho is a type 1 transmembrane anti-aging protein. αKlotho-deficient mice have premature aging phenotypes and an imbalance of ion homeostasis including Ca2+ and phosphate. Soluble αKlotho is known to regulate multiple ion channels and growth factor-mediated phosphoinositide-3-kinase (PI3K) signaling. Store-operated Ca2+ entry (SOCE) mediated by pore-forming subunit Orai1 and ER Ca2+ sensor STIM1 is a ubiquitous Ca2+ influx mechanism and has been implicated in multiple diseases. However, it is currently unknown whether soluble αKlotho regulates Orai1-mediated SOCE via PI3K-dependent signaling. Among the Klotho family, αKlotho downregulates SOCE while βKlotho or γKlotho does not affect SOCE. Soluble αKlotho suppresses serum-stimulated SOCE and Ca2+ release-activated Ca2+ (CRAC) channel currents. Serum increases the cell-surface abundance of Orai1 via stimulating vesicular exocytosis of the channel. The serum-stimulated SOCE and cell-surface abundance of Orai1 are inhibited by the preincubation of αKlotho protein or PI3K inhibitors. Moreover, the inhibition of SOCE and cell-surface abundance of Orai1 by pretreatment of brefeldin A or tetanus toxin or PI3K inhibitors prevents further inhibition by αKlotho. Functionally, we further show that soluble αKlotho ameliorates serum-stimulated SOCE and cell migration in breast and lung cancer cells. These results demonstrate that soluble αKlotho downregulates SOCE by inhibiting PI3K-driven vesicular exocytosis of the Orai1 channel and contributes to the suppression of SOCE-mediated tumor cell migration. [ABSTRACT FROM AUTHOR]

Posttraumatic hydrocephalus (PTH) is common in patients undergoing decompressive craniectomy (DC) for traumatic brain injury (TBI), but the incidence, mechanisms, and risk factors have not been fully elucidated. This study aimed to determine the incidence of and the factors associated with PTH. We retrospectively reviewed patients who underwent DC for TBI at our institute between January 2014 and December 2018. We identified and compared the demographic, clinical, and radiological data, and 12-month functional outcome (as assessed by the Glasgow Outcome Scale [GOS]) between patients who developed PTH and those who did not. Logistic regression analyses were performed to identify risk factors for PTH. Additionally, the influence of PTH on unfavorable functional outcome was analyzed. PTH developed in 18 (18.95%) of the 95 patients who survived at 1 month after DC. A multivariate analysis indicated that postoperative intraventricular hemorrhage (odds ratio [OR] 4.493, P = 0.020), postoperative subdural hygroma (OR 4.074, P = 0.021), and postoperative hypothermia treatment (OR 9.705, P = 0.010) were significantly associated with PTH. The 12-month functional outcome significantly differed between the patients who developed PTH and those who did not (P = 0.049). Patients who developed PTH had significantly poorer 12-month functional outcomes than those who did not (P = 0.049). Another multivariate analysis indicated that subdural hemorrhage (OR 6.814, P = 0.031) and the presence of at least one dilated pupil before DC (OR 8.202, P = 0.000) were significantly associated with unfavorable functional outcomes (GOS grades 1–3). Although the influence of PTH (OR 5.122, P = 0.056) was not statistically significant in the multivariate analysis, it had a great impact on unfavorable functional outcomes. PTH considerably affects functional outcomes at 12 months after DC for TBI. Furthermore, postoperative imaging findings such as intraventricular hemorrhage and subdural hygroma can predict the development of PTH; therefore, careful observation is required during the follow-up period. [ABSTRACT FROM AUTHOR]

Background: Although the dopaminergic system is interconnected with the hypothalamic-pituitary-thyroid axis, few studies have explained the causal relationship between thyroid disease and Parkinson's disease (PD). Objective: The goal of this study was to investigate the association between thyroid diseases and PD in Korean residents. Methods: The Korean National Health Insurance Service-National Sample Cohort, which includes individuals aged ≥40 years, was assessed from 2002 to 2015. A total of 5,586 PD patients were matched by age, sex, income, and the region of residence with 22,344 control participants at a ratio of 1:4. In the PD and control groups, previous histories of levothyroxine treatment, goiter, hypothyroidism, thyroiditis, and hyperthyroidism were investigated. Results: The rates of levothyroxine treatment for more than 3 months, hypothyroidism, and hyperthyroidism were higher in the PD group than the control group (3.2%, 3.8%, and 2.8% vs. 2.5%, 2.9%, and 1.9%, respectively, p < 0.05). The adjusted odds ratios (ORs) in model 2, which was adjusted for all potential confounders, for hypothyroidism and hyperthyroidism in the PD group were 1.25 (95% confidence interval (CI) 1.01–1.55, p = 0.044) and 1.37 (95% CI 1.13–1.67, p = 0.002), respectively. In subgroup analyses, the association between hypothyroidism and PD was maintained in men older than 70 years and the association between hyperthyroidism and PD was maintained in women younger than 70 years. Conclusion: Both hyperthyroidism and hypothyroidism were associated with higher risk of PD, particularly for women younger than 70 years and men older than 70 years, respectively. [ABSTRACT FROM AUTHOR]

Only a few studies have reported nontraumatic intracerebral hemorrhage in young patients notwithstanding its fatal and devastating characteristics. This study investigated the clinical characteristics and outcome of nontraumatic intracerebral hemorrhage in young patients in comparison to those of the elderly. A retrospective review of consecutive patients admitted at the department of neurosurgery of two tertiary care medical centers presenting with first-ever nontraumatic intracerebral hemorrhage was performed. We identified and compared the demographics, etiologies, risk factors, and laboratory, radiological, and clinical findings between elderly and young patients. Additionally, logistic regression analyses of independent prognostic factors associated with 1-month mortality and favorable functional outcome were performed. Altogether, 247 patients including 69 young patients and 178 elderly patients were enrolled. On multivariate analysis, young patients exhibited significantly more often an infratentorial hematoma location, excessive alcohol consumption, and high body mass index (BMI), but less frequent systemic hypertension. There was no statistical difference between the two groups in 1-month mortality (17.46% and 18.01% for young and elderly patients, respectively), but the favorable functional outcome based on modified Rankin scale score of 0 or 1 was significantly different between the two groups (favorable outcome in 51.79% and 29.93% of patients, respectively). Predictors of 1-month mortality was the presence of herniation in the young group, and lower Glasgow Coma Scale score, renal or heart disease, and leukocytosis (WBC > 10,000) in the elderly group. Lower National Institutes Health Stroke Scale score was associated with favorable functional outcome in both groups. Nontraumatic intracerebral hemorrhage in younger patients appears to be associated with excessive alcohol consumption and high BMI. Younger patients had similar short-term mortality but more favorable functional outcome than the elderly. [ABSTRACT FROM AUTHOR]

We report on polarization-dependent transient carrier dynamics and coherent phonon oscillations in single-walled carbon nanotubes by determining the relation between the nanotube axis and the incident light polarization. Due to the anisotropic shape of nanotubes, optical absorption strongly depends on the polarization direction. We observed three decay components when the excitation wavelength was resonant with the E22 transition energy and observed two-decay components under off-resonance conditions. The transient absorption and coherent phonon amplitudes were measured as a function of the angle between the pump and probe polarizations and were analyzed based on the absorption anisotropy of carbon nanotubes. [ABSTRACT FROM AUTHOR]

We report the observation of a coherent nonlinear signal in pump-probe experiments on a ferromagnetic GaMnAs. The coherent signal, which is originating due to coherent interaction between pump and probe beams, depends on the polarization configuration of each beam and follows the sample magnetization as it changes with the applied magnetic field and/or the sample temperature. [ABSTRACT FROM AUTHOR]

Morphology evolution of asperity contacts in microelectromechanical systems switches is examined in the framework of the phase field method. Surface mass diffusion, driven by capillarity, rapidly increases the asperity contact radius at early times, decreases it slowly at later times, and, possibly, pinches off the contact due to a Rayleigh instability. Electromigration accelerates this process but retards or prevents the pinch off at late times. The evolution occurs faster when the asperity size and/or density are smaller. Approximate analytical results for the evolution kinetics are provided. [ABSTRACT FROM AUTHOR]

There is no consensus on a standardized approach to spasticity or dystonia management of cerebral palsy (CP). This study aimed to investigate clinical outcomes and compare therapeutic responses for pallidal stimulation versus intrathecal baclofen (ITB) therapy in adult patients with severe CP. We retrospectively reviewed patients with CP treated with deep brain stimulation (DBS) of the globus pallidus internus (GPi) or implantation of ITB pump between June 2003 and April 2017. Patients were included if they were clinically diagnosed with medically intractable CP and had >12 months of postprocedural follow-up data. Patients were assessed before and 12 months post-treatment using the visual analogue scale, Burke–Fahn–Marsden Dystonia Rating Scale, self-rating improvement scale, and 36-Item Short-Form General Health Survey Questionnaire. Patients (n = 22) were divided into GPi DBS (n = 12) and ITB therapy (n = 10) groups. For the Burke–Fahn–Marsden Dystonia Rating Scale, DBS group movement scores and ITB group disability scores were significantly improved post-treatment. Although visual analogue scales did not differ between groups, self-rating improvement scores differed significantly between groups. For quality of life, physical functioning, body pain, vitality, social functioning, and mental health significantly improved in ITB group 12 months post-treatment compared with those of preoperative period. Only mental health differed significantly between groups. Despite retrospective design and relatively low number of cases, this study indicated that ITB therapy was less invasive and more effective in improving the quality of life compared with GPi DBS. ITB therapy should be considered an alternative treatment for patients with severe CP. [ABSTRACT FROM AUTHOR]

Objective. This study was performed to assess neurosurgery patients' preference for surgeon's attire and appearance in the hospital. Methods. A total of 100 patients were investigated using a questionnaire comprising 13 questions. We first asked patients about neurosurgeon's appearance including accessories, hair color, mustache, and beard. Then, based on their preferences, they were asked to rank a series of photographs which illustrated a variety of neurosurgeon attires worn by a doctor. Results. Professional attire with white coat was the most ideal for patients compared to any other attire (preference scale 5.28 ± 1.24), and there was a significant preference gap between wearing a white coat and not wearing a white coat (p <0.01). Patients expressed a preference for neurosurgeon's shoes (30%) but the majority of the respondents answered that it does not matter which shoes their neurosurgeon wears (43%). Furthermore, the patients did not have any preferences regarding accessories, dyeing, and mustache or beard (58%, 67%, and 51%, respectively), and they did not have negative view towards doctor wearing accessories (71.7%) and growing mustache or beard (71.6%). Conclusion. The patients in this study preferred professional attire along with a white coat compared to any other form of outfit. This result is similar to those of many other studies conducted in other departments or other countries. However, patients did not have a strong negative view on accessories, dyeing, and facial hair. With regard to medical training, patients did not show a preference for their neurosurgeon's educational background. [ABSTRACT FROM AUTHOR]

Despite growing interest in the preventive effects of statins, as lipid-lowering agents, on migraine attacks, comprehensive nationwide studies comparing migraine likelihood between statin users and controls are lacking. Our nested case–control study within the Korean National Health Insurance Service-Health Screening Cohort (2002–2019) investigated this association using 38,957 migraine patients and 155,828 controls, considering migraine subtypes (with/without aura) and statin types (lipophilic vs. hydrophilic). Using propensity score matching and adjusting for confounders, statin use was linked to reduced migraine likelihood overall (odds ratio (OR) 0.93), particularly for migraines with aura (OR 0.75) and without aura (OR 0.94). Lipophilic statins were effective for both subtypes, while hydrophilic statins mainly reduced the likelihood of migraines without aura. Subgroup analyses showed consistent benefits across demographics, but varied effectiveness based on weight, smoking, alcohol use, hemoglobin levels, and dyslipidemia history. In summary, this nationwide cohort study suggests that statin use may reduce migraine likelihood among Korean adults across diverse demographics and clinical profiles, but varied effectiveness based on certain lifestyle and comorbidity factors underscores the importance of considering individual patient profiles when assessing the potential benefits of statin therapy for migraine prevention. [ABSTRACT FROM AUTHOR]

Recent studies have reported chronic rhinosinusitis (CRS) as an independent risk factor for stroke. However, the association with stroke depending on the affected sinuses has not been explored. This study aimed to elucidate the side- and sinus-specific relationship between CRS and ischemic stroke through imaging analyses. We retrospectively reviewed the medical records of patients who were diagnosed with ischemic stroke at a tertiary center. CRS was defined as having a total score of greater than or equal to 4, according to the Lund–Mackay scoring system, through brain magnetic resonance imaging or computed tomography. We investigated the side- and sinus-specific correlation between CRS and ischemic stroke. Subgroup analyses were performed for different age groups. CRS prevalence in patients with ischemic stroke was 18.4%, which was higher than the previously reported prevalence in the general population. Overall, there was no correlation between the directions of the CRS and ischemic stroke (p > 0.05). When each sinus was analyzed, the frontal (Cramer's V = 0.479, p < 0.001), anterior (Cramer's V = 0.396, p < 0.001)/posterior (Cramer's V = 0.300, p = 0.008) ethmoid, and sphenoid (Cramer's V = 0.383, p = 0.005) sinuses showed a statistically significant correlation with the side of stroke, but the maxillary sinus (Cramer's V = 0.138, p = 0.208) did not. In subgroup analyses, a significant right-side correlation between the two diseases was observed in the older-age subgroup (≥65 years old, Cramer's V = 0.142, p = 0.040). Diabetes mellitus (odds ratio = 1.596, 95% confidence interval = 1.204–2.116) was identified as an independent risk factor for having CRS in patients with ischemic stroke. CRS of the frontal, anterior/posterior ethmoid, and sphenoid sinuses has a directional relationship with ischemic stroke. Our results on which sinuses correlate with stroke advocate for the active surveillance of CRS in patients at high risk of ischemic stroke. [ABSTRACT FROM AUTHOR]

Wound healing is a physiological restorative response to tissue and cell injury. This process occurs in collaboration with a complex cascade of cellular events, including biochemical alterations to the extracellular matrix. Polydeoxyribonucleotide (PDRN) is a fragmented DNA mixture from Oncorhynchus mykiss or Oncorhynchus keta sperm known to promote tissue regeneration under different pathophysiological conditions. However, the most effective molecular size of PDRNs for promoting the wound healing process and quality has not been established. In the present study, the regeneration quality with low (<50 kDa), middle [classic PDRN; 50–1,500 kDa] and high (>1,500 kDa) molecular weight PDRNs in a skin wound healing mouse model was examined using hematoxylin and eosin, as well as Masson's trichrome stain. A 4 mm biopsy punch was used to produce wounds in the skin of the mice. PDRN-mediated cellular behavior and signaling were evaluated by in vitro scratch assay and western blot analysis, respectively. It was observed that the apparent surface wound healing processes were not significantly different between PDRN molecular sizes. Immunohistochemical analysis revealed that classic PDRN-injected mice exhibited less lipid accumulation with increased collagen composition. These results suggested that 50–1,500 kDa PDRN offers an effective DNA mixture to improve wound healing quality. Furthermore, classic PDRN increased cell migration via c-Jun N-terminal kinase signaling in human fibroblasts. The present study suggests an optimal PDRN molecular weight to promote wound healing, and novel approaches for therapeutic strategies to improve tissue regeneration quality. [ABSTRACT FROM AUTHOR]

Purpose. The purpose of this study was to investigate the association of exercise capacity, cardiac function, and coronary artery calcification (CAC) with components of metabolic syndrome in Korean adults. Method. Medical records of healthy adults who underwent exercise tolerance test (ETT), coronary CT angiography (CTA), and echocardiography of the heart for cardiac health check-up were retrospectively reviewed. Patients who had a history of severe cardiovascular disease or could not perform ETT due to other musculoskeletal problems were excluded. Subjects were classified into groups based on the number of components for metabolic syndrome: no component (Group 1, n=90), 1, 2 components (Group 2, n=321), and 3 or more components (Group 3, n=154). Exercise capacity was assessed using the symptom-limited ETT, and CAC score was obtained using the coronary CTA and Agatston score. Cardiac structure and function were assessed using echocardiography. Results. A total of 565 patients (mean (SD) age 59.5 (9.1), 340 men, 225 women) were selected. Exercise capacity was significantly lower in Group 3 than in the other groups (p<0.05). The CAC score was significantly higher in Group 3 than in the other groups (p<0.05). Compared to the other groups, echocardiography findings in Group 3 showed a greater hypertrophy of the left ventricle and reduction in the diastolic function (p<0.05). Exercise capacity, CAC score, cardiac structure, and function were different between the 3 groups, where a tendency to worsen was observed from Group 1 to Group 3. Conclusion. Metabolic syndrome decreases exercise capacity of the patient and contributes to CAC, thereby increasing the risk for cardiovascular diseases and deterioration in cardiac structure and function. Therefore, early detection of metabolic syndrome and subsequently the prevention and management of heart disease are necessary. [ABSTRACT FROM AUTHOR]

Background Zonulin is acknowledged as the only physiological mediator established to reversibly regulate intestinal permeability through modulation of intercellular tight junctions. We aimed to determine whether there are differences in zonulin levels between 74 subjects with overweight or obesity and 76 with normal-weight and to assess correlations of circulating zonulin levels with anthropometric measures and obesity-related biomarkers. Methods We assessed anthropometric and laboratory measures, including body mass index (BMI) z-score, blood pressure, liver enzymes, lipid profiles, and insulin resistance. Serum zonulin levels were measured using an enzyme-linked immunosorbent assay. Results The mean age of the participants was 12.8 ± 1.5 years. Circulating serum zonulin levels were significantly increased in subjects with overweight/obesity compared with those of normal-weight ( P  = 0.03). Zonulin levels were significantly and positively associated with BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P  < 0.05). In multivariate linear regression analysis, alanine aminotransferase was significantly and positively associated with circulating zonulin levels in adolescents with overweight or obesity ( P  < 0.01) after controlling for the effect of potential confounding factors. BMI z-score tended to be positively associated with serum zonulin levels in this subgroup analysis ( P  = 0.06). Conclusions Serum zonulin is a biomarker associated with hepatic metabolic disturbances in young adolescents with overweight or obesity. The positive relationship suggests a potentially relevant pathophysiological mechanism linking zonulin to hepatic metabolism in this age group of young adolescents with overweight or obesity. [ABSTRACT FROM AUTHOR]

Given the global significance of gout and gastric cancer (GC) as major health problems with interrelated impacts, we examined the development of GC in Korean patients with gout. We conducted a nested case–control study using data from 10,174 GC patients and 40,696 control patients from the Korean National Health Insurance Service-National Sample Cohort database. Propensity score matching (1:4) with propensity score overlap-weighted adjustment was used to reduce selection bias and estimate the odds ratio (OR) and 95% confidence intervals (CIs) for the association between gout and GC. An adjusted OR for GC was not significantly higher in patients with gout than in control patients (1.02; 95% CI, 0.93–1.12; p = 0.652). Additionally, no association between gout and GC was observed in subgroup analyses such as sex, age, level of income, region of residence, or Charlson Comorbidity Index score. In conclusion, these results suggest that gout is not a significant independent risk factor for GC among the Korean population. Additional investigation is required to establish a causal association between gout and GC, and to generalize these results to general populations. [ABSTRACT FROM AUTHOR]

Objective Gamma Knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) introduces risks to the facial nerve and auditory perception and may involve post-treatment complications such as pseudoprogression, hydrocephalus, and other cranial neuropathies. This study of patients with VS who underwent GKS investigated radiosurgical results, focusing on post-treatment complications and identifying the factors that predict such complications. Methods We undertook a retrospective review of all VS patients treated with the Perfexion Leksell Gamma Knife between November 2007 and October 2010 at our institution. Patients who underwent at least 12 months of clinical and radiologic assessments before and after GKS were included. Results All 235 patients were included in the analyses reported here. The 5-year serviceable hearing and facial nerve preservation values were 73.9% and 94.3%, respectively. Following GKS, 43 patients (18.30%) showed pseudoprogression, 15 (6.38%) exhibited hydrocephalus, 22 (9.36%) showed trigeminal neuropathy, 14 (5.96%) showed vertigo, and 25 (10.64%) showed facial myokymia. According to multivariate analysis, solid tumor nature was significantly associated with pseudoprogression and patient age was significantly associated with hydrocephalus. Patients receiving margin doses ≥13 Gy had a significantly higher probability of loss of serviceable hearing. Patients with smaller tumors had a trigeminal nerve preservation rate comparable with patients harboring larger tumors. Patients receiving margin doses <13 Gy or older patients had a significantly higher probability of vestibular nerve dysfunction. Conclusions Further prospective studies should be designed to provide further insight into the exact relationship between the predictive factors we investigated and post-treatment complications. [ABSTRACT FROM AUTHOR]

Aims: The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated. Results: HO-1 and VEGF were coexpressed in astrocytes of ischemic mouse brain tissues. Experiments with specific siRNAs and pharmacological activators/inhibitors of various target genes demonstrated that astrocytes pre-exposed to the CO-releasing compound, CORM-2, or transfected with HO-1 increased HIF-1α-independent VEGF expression via sequential activation of the following signal cascades; Ca2+/calmodulin-dependent protein kinase kinase β-mediated AMP-activated protein kinase (AMPK)α activation, AMPKα-induced increases in nicotinamide phosphoribosyltransferase (NAMPT) expression and cellular NAD+ level, sirtuin 1 (SIRT1)-dependent peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) stabilization and activation, and PGC-1α/estrogen-related receptor (ERR)α-mediated VEGF expression. All of these sequential events were blocked by an L-type voltage-gated Ca2+ channel inhibitor and Ca2+ chelators, but not by other Ca2+ channel inhibitors. Innovation: HO-1-derived CO elicits Ca2+ influx by activating L-type Ca2+ channels, which is a key player in HIF-1α-independent VEGF expression by activating the AMPKα-NAMPT-SIRT1-PGC-1α/ERRα pathway. Conclusion: Our results provide new mechanistic insight into the possible role for L-type Ca2+ channels in HO-1/CO-induced angiogenesis. Antioxid. Redox Signal. 27, 21-36. [ABSTRACT FROM AUTHOR]

We report a chemical bath deposition approach for the preparation of large arrays of oriented ZnO nanostructures by activated substrate processes, and precipitated ZnO nanorods by passive occupation of the crystal surface. Photoluminescence dynamics showed that various visible emission characteristics associated with defects such as oxygen vacancy, zinc interstitial or their complexes. In addition, the precipitated ZnO nanorods exhibited excellent performance in the adsorption and photocatalytic decomposition of organic dyes, achieving 95% photodegradation of Rhodamine 6B. Moreover, oxygen defects function as trap sites with strong adsorption abilities towards organic dyes and showed high performance in the photocatalytic degradation of the dye molecules. [ABSTRACT FROM AUTHOR]

Two new phenolic compounds, methyl 2-hydroxy-4-methoxy-6-(2-oxopentyl)-benzoate (1) and 4-methoxy-6-pentyl-1,2-dihydroxybenzene (2), together with two known phenolic derivatives, were isolated from the Antarctic lichen Pertusaria dactylina (Pertusariaceae). The structures of the new compounds were determined by 1D and 2D NMR and HR-MS experiments, as well as by comparison of their data with the published values. [ABSTRACT FROM AUTHOR]

Single layer semiconductor transition metal dichalcogenides (TMDs) possess outstanding properties that are desirable for development of 2D nanoelectronics and optoelectronics. One of outstanding properties is large exciton and trion binding energy rendering them to be stable even at room temperature, which governed nearly all optical characteristics observed in monolayer TMDs. However, behaviors of excitons and trions are very sensitive to external factors, including strain, dielectric of surrounding environment, electrical and chemical doping, and temperature. These features provide various approaches to manipulate in controllable manner optical and electronic properties of monolayer TMDs and their in-depth understanding is essential to exploit them for future optoelectronic devices. Here we review basic exciton properties and the impacts of charged doping, strain, dielectric screening, temperature and excitation intensity on excitonic behaviors reflected via photoluminescence spectra for monolayer of TMDs. [ABSTRACT FROM AUTHOR]

A correction to the article "Capillarity and electromigration effects on asperity contact evolution in microelectromechanical systems switches" that was published in a previous issue is presented.

• A novel iterative least squares method for continuous piecewise linear fitting. • Constrained least squares is used to guarantee the continuity. • Gradient descent with momentum is used for better convergence. • Proposed method requires less computational complexity than the existing methods. In this work, a novel iterative least squares method is proposed to approximate nonlinear functions with continuous piecewise linear (CPWL) functions, where the continuity is guaranteed by constrained least squares. A typical least-squares-based method for CPWL fitting consists of two major steps: to perform least squares for a fixed set of breakpoints (i.e. for a specific partition of function domain), and to update breakpoints to reduce the overall fitting error. The proposed method aims to improve the existing CPWL method, the one with canonical representation, by modifying both major steps. Instead of performing ordinary least squares with canonical representation, partitioned least squares and constrained least squares are successively performed to reduce the computational complexity. For the update of breakpoints, an iterative procedure is proposed, where gradient descent with momentum method is employed to improve the convergence characteristics. The advantages of proposed method are illustrated using illustrative examples. [ABSTRACT FROM AUTHOR]

Regulation of ATP-sensitive inwardly rectifying potassium (K ATP ) channel plays a critical role in metabolism-secretion coupling of pancreatic β-cells. Released insulin from β-cells inhibits insulin and glucagon secretion with autocrine and paracrine modes. However, molecular mechanism by which insulin inhibits hormone secretion remains elusive. Here, we investigated the effect of autocrine insulin on surface abundance of K ATP channel in mouse clonal β-cell line, MIN6. High glucose increased plasmalemmal sulfonylurea receptor 1 (SUR1), a component of K ATP channel as well as exogenous insulin treatment. SUR1 trafficking by high glucose or insulin was blocked by inhibition of phosphoinositide 3-kinase (PI3K) with wortmannin. Pretreatment with brefeldin A or silencing of vesicle-associated membrane protein 2 (VAMP2) abolished insulin-mediated upregulation of surface SUR1. Functionally, glucose-stimulated cytosolic Ca 2+ ([Ca 2+ ] i ) increase was blunted by insulin or diazoxide, a K ATP channel opener. Insulin-induced suppression of [Ca 2+ ] i oscillation was prevented by an insulin receptor blocker. These results provide a novel molecular mechanism for autocrine negative feedback regulation of insulin secretion. [ABSTRACT FROM AUTHOR]

Histone acetylation has been known to be significant in spermatogenesis. Histone acetylation is regulated by the act of histone deacetylases (HDACs) and histone acetyltransferases (HATs). We investigated the link between expression levels of HDACs and HATs in mouse sperm and subsequent blastocyst formation rate. In the univariate analysis, expression levels of HDAC1 and HAT were generally not associated with the blastocyst formation rate. When divided by the mature oocyte number category, a significant positive association was observed between the expression levels of HDAC1 and the blastocyst-forming rate in the highest (> 75th) percentile group (a group with ≥34 mature oocytes). In conclusion, expression of sperm HDAC1 could be considered as a possible predictor of embryo development in mice with high ovarian response. [ABSTRACT FROM AUTHOR]

The effects of irradiance and temperature on growth and flowering in seed propagated Sinningia cardinalis especially to increase the number of flowers were investigated. To understand the effect of irradiance on flowering and the number of flowers, seedlings were grown under 30% shade (30% SH), natural irradiance (ND), and ND supplemented with 14 h of high irradiance at 14 W/m 2 (ND + 14HID) at 3 stages (ST) lasted for 40 days (d) at each ST (Expt. 1). Flowering was the earliest (205 d) when 20-d old plants were grown under 30% SH during the entire three stages (July 1 through October 31). Longer than 215 d to flower was required when plants received ND + 14HID during stage 3 (ST 3) (September 21–October 31). The number of flowers was highest (22) when grown under 30% SH during ST 1 (July 1–August 10) followed by ND or ND + 14HID during the ST 2 (August 12–September 20) or ST 3. To investigate the effect of temperature on flowering and the number of flowers, 42 d of 15/13 °C (15 °C), 19/17 °C (19 °C), 23/21 °C (23 °C), and 27/25 °C (27 °C) and under ND + 10HDI were given to 45-d old plants (Expt. 2). The number of days to flower was only significantly accelerated at 23° and 27 °C as compared to 15 °C and 19 °C, but not by irradiance treatments. The highest number of flowers (24) was produced when plants were grown at 15 °C under ND + 10HID given prior to formation of three pairs of leaves (<3L). To further refine the level of reduced of light irradiance on the number of flowers, plants were grown under 45% shade (45% SH), 30% shade (30% SH) from 08:00 to 20:00 h, and ND were given to 128-d old plants between days 0 and 20 (0 and 20), 21 and 40, and 0 and 40 (Expt. 3). The number of flowers (17.6) was significantly increased when grown under 45% SH, especially during the 21–40 d period. To investigate the effect of temperature on plants at visible buds stages, plants were transferred to growth chambers maintained at 18, 21, 24, 27, and 30 °C during the day (0800–1600 h; 35 W/m 2 ) and at 16 °C at night for 42 d (Expt. 4). Flowering was delayed from 100 to 115 d as day temperatures were increased from 18° to 30 °C, and the number of flowers was the highest number (26.5 flowers) at 24 °C. Therefore, to promote flowering and to increase the flower numbers, S. cardinalis should be grown under 30% SH or under ND photoperiod during May–October. At a later stage of flower bud development, temperature rather than irradiance controls the speed of flowering. The differences in flowering time for only 16 d from sowing to flowering may suggest that S. cardinalis can be considered as a day-neutral plant for flower bud initiation. [ABSTRACT FROM AUTHOR]

REDD1 is induced by various cellular stresses; however, its expression in response to lipopolysaccharide (LPS) has not been clearly elucidated in immune cells. LPS stimulated CREB-dependent and NF-κB-independent REDD1 expression in macrophages. Early increases in CREB phosphorylation and REDD1 expression at 8 h following LPS treatment were blocked by inhibition of p38MAPK and mitogen- and stress-activated protein kinase 1 (MSK1), but not PKA. However, delayed CREB-mediated REDD1 expression at 16 h was suppressed by inhibition of cyclooxygenase-2 (COX-2) and PKA. It indicates that LPS induces REDD1 expression by two distinct CREB-mediated mechanisms, the early p38MAPK/MSK1 and the delayed COX-2/PGE 2 /PKA pathways. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to identify the risk factors of twin gestation in fresh double day-3 embryo transfer cycles. Material and Methods Out of a total of 386 cycles of fresh double embryo transfers on day 3 between 2006 and 2013 at a single center, 72 women with single intrauterine gestational sac (GS) (single-GS group) and 32 women with double GS (double-GS group) were identified. The patients' clinical characteristics and laboratory results were extracted from electronic medical records and were compared. Results The double-GS group had a significantly younger age ( P = 0.012), and higher bodyweight ( P = 0.033) compared with the single-GS group. The total number of blastomeres ( P = 0.013) and cumulative embryo score ( P = 0.012) were higher in the double-GS group. By receiver-operator curve analysis, maternal age ≤ 35 years, maternal bodyweight > 60 kg, total number of blastomeres > 14, and cumulative embryo score > 49 were the cut-off values to predict twin pregnancy. Among eight women with all four risk factors, the twin pregnancy rate was 87.5%. There was no twin pregnancy among seven women with no risk factors. Conclusion Younger age, higher bodyweight, and better embryo quality are all associated with a higher incidence of twin pregnancy after double embryo transfer on day 3. Single embryo transfer might be advisable for couples with risk factors for twin pregnancy. [ABSTRACT FROM AUTHOR]

Aims: Hypoxia induces expression of various genes and microRNAs (miRs) that regulate angiogenesis and vascular function. In this study, we investigated a new functional role of new hypoxia-responsive miR-101 in angiogenesis and its underlying mechanism for regulating heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) expression. Results: We found that hypoxia induced miR-101, which binds to the 3′untranslated region of cullin 3 (Cul3) and stabilizes nuclear factor erythroid-derived 2-related factor 2 (Nrf2) via inhibition of the proteasomal degradation pathway. miR-101 overexpression promoted Nrf2 nuclear accumulation, which was accompanied with increases in HO-1 induction, VEGF expression, and endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) production. The elevated NO-induced S-nitrosylation of Kelch-like ECH-associated protein 1 and subsequent induction of Nrf2-dependent HO-1 lead to further elevation of VEGF production via a positive feedback loop between the Nrf2/HO-1 and VEGF/eNOS axes. Moreover, miR-101 promoted angiogenic signals and angiogenesis both in vitro and in vivo, and these events were attenuated by inhibiting the biological activity of HO-1, VEGF, or eNOS. Moreover, these effects were also observed in aortic rings from HO-1+/− and eNOS−/− mice. Local overexpression of miR-101 improved therapeutic angiogenesis and perfusion recovery in the ischemic mouse hindlimb, whereas antagomiR-101 diminished regional blood flow. Innovation: Hypoxia-responsive miR-101 stimulates angiogenesis by activating the HO-1/VEGF/eNOS axis via Cul3 targeting. Thus, miR-101 is a novel angiomir. Conclusion: Our results provide new mechanistic insights into a functional role of miR-101 as a potential therapeutic target in angiogenesis and vascular remodeling. Antioxid. Redox Signal. 21, 2469-2482. [ABSTRACT FROM AUTHOR]

Human deciduous and permanent teeth exhibit different developmental processes, morphologies, histological characteristics and life cycles. In addition, their pulp tissues react differently to external stimuli, such as the pulp sensitivity test, dental trauma and pulp therapy materials. These suggest differences in gene expression and regulation, and in this study we compared gene-expression profiles of the human dental pulp from deciduous and permanent teeth. Pulp tissues from permanent premolars and deciduous molars aged 11–14 years were extirpated and mRNA was isolated for cDNA microarray analysis, and quantitative real-time PCR (qPCR). Other teeth were used for immunohistochemical analysis (IHC). Microarray analysis identified 263 genes with a twofold or greater difference in expression level between the two types of pulp tissue, 43 and 220 of which were more abundant in deciduous and permanent pulp tissues, respectively. qPCR analysis was conducted for eight randomly selected genes, and the findings were consistent with the cDNA microarray results. IHC confirmed that insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was broadly expressed in deciduous dental pulp tissue, but minimally expressed in permanent dental pulp tissue. Immunohistochemical analysis showed that calbindin 1 (CALB1), leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), and gamma-aminobutyric acid A receptor beta 1 (GABRB1) were abundantly expressed in permanent predentin/odontoblasts, but only minimally expressed in deciduous dental pulp tissue. These results show that deciduous and permanent pulp tissues have different characteristics and gene expression, suggesting that they may have different functions and responses to therapies focused on pulp or dentin regeneration. [ABSTRACT FROM AUTHOR]

Highlights: [•] Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. [•] Orai1 and STIM1 constitute a native store-operated Ca2+ entry in ccRCC cells. [•] Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. [ABSTRACT FROM AUTHOR]

Abstract: TRPV5 and TRPV6 channels are expressed in distal renal tubules and play important roles in the transcellular Ca2+ reabsorption in kidney. They are regulated by multiple intracellular factors including protein kinases A and C, membrane phospholipid PIP2, protons, and divalent ions Ca2+ and Mg2+. Here, we report that fluid flow that generates shear force within the physiological range of distal tubular fluid flow activated TRPV5 and TRPV6 channels expressed in HEK cells. Flow-induced activation of channel activity was reversible and did not desensitize over 2min. Fluid flow stimulated TRPV5 and 6-mediated Ca2+ entry and increased intracellular Ca2+ concentration. N-glycosylation-deficient TRPV5 channel was relatively insensitive to fluid flow. In cells coexpressing TRPV5 (or TRPV6) and Slo1-encoded maxi-K channels, fluid flow induced membrane hyperpolarization, which could be prevented by the maxi-K blocker iberiotoxin or TRPV5 and 6 blocker La3+. In contrast, fluid flow did not cause membrane hyperpolarization in cells coexpressing ROMK1 and TRPV5 or 6 channel. These results reveal a new mechanism for the regulation of TRPV5 and TRPV6 channels. Activation of TRPV5 and TRPV6 by fluid flow may play a role in the regulation of flow-stimulated K+ secretion via maxi-K channels in distal renal tubules and in the mechanism of pathogenesis of thiazide-induced hypocalciuria. [Copyright &y& Elsevier]