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AbstractThere are many ways for zero-dividing polynomials to go up to zero-dividing ideals when the base rings are IFP. The importance of these in ring theory leads us to consider the following ring conditions and study new useful roles of matrices for ring theory. Let R be a ring and a,b∈R\{0}. The first is the condition (*) that if ab = 0 then Ib = 0 for some nonzero ideal I⊆RaR of R or aJ = 0 for some nonzero ideal J⊆RbR of R. It is shown that from given any IFP ring, there can be constructed a non-IFP ring with the condition (*). We prove that a semiprime ring R with the condition (*) is both right and left nonsingular. The second is the condition (**) that if ab = 0 then IJ = 0 for some nonzero ideals I⊆RaR and J⊆RbR of R. We prove that every ring can be a subring of rings with the condition (**), that if R is an irreducible ring with the condition (**) then R is either a domain or non-semiprime, and that the condition (**) passes to polynomial rings when the base ring is semiprime. Various sorts of examples are given to illustrate and delimit the results obtained. [ABSTRACT FROM AUTHOR]

Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. The progression of sarcopenia is correlated with the onset of physical disability, the inability to live independently, and increased mortality. Due to global increases in lifespan and demographic aging in developed countries, sarcopenia has become a major socioeconomic burden. Clinical therapies for sarcopenia are based on physical therapy and nutritional support, although these may suffer from low adherence and variable outcomes. There are currently no clinically approved drugs for sarcopenia. Consequently, there is a large amount of pre-clinical research focusing on discovering new candidate drugs and novel targets. In this review, recent progress in this research will be discussed, along with the challenges that may preclude successful translational research in the clinic. The types of drugs examined include mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates. In light of the large number of drugs and targets being reported, it can be envisioned that clinically approved pharmaceuticals to prevent the progression or even mitigate sarcopenia may be within reach. [ABSTRACT FROM AUTHOR]

In a power plant that uses seawater as a coolant, a debris filter (DF) is required to remove foreign substances from the seawater, and differential pressure leads to a decrease in the coolant flow rate, leading to a decrease in the power generation efficiency. In this study, an analysis was performed for the cases wherein the initial flow velocity conditions of the DF used in the condenser tube cleaning system (CTCS) were 1.5 m/s, 2.0 m/s, and 2.5 m/s using Ansys Fluent 2021, and the flow characteristics were identified. The flow and differential pressure characteristics of a CTCS with an installed DF were considered in a comparative analysis of the velocity, pressure, and turbulence kinetic energy (TKE) distributions. The results confirmed that a vortex was generated in the pipe with the DF, apparently due to the collision of the flow with the bracket of the DF. As the flow rate increased, the range of the vortex increased, causing a loss in flow. [ABSTRACT FROM AUTHOR]

In this study, we focused on confirming the steroid hormone receptor-mediated endocrine-disrupting potential of the pyrethroid insecticide fenvalerate and unraveling the underlying mechanisms. Therefore, we assessed estrogen receptor-α (ERα)- and androgen receptor (AR)-mediated responses in vitro using a hormone response element-dependent transcription activation assay with a luciferase reporter following the Organization for Economic Cooperation and Development (OECD) test guidelines. We observed that fenvalerate acted as estrogen by inducing the translocation of cytosolic ERα to the nucleus via ERα dimerization, whereas it exhibited no AR-mediated androgen response element-dependent luciferase activity. Furthermore, we confirmed that fenvalerate-induced activation of ERα caused lipid accumulation, promoted in a fenvalerate-dependent manner in 3 T3-L1 adipocytes. Moreover, fenvalerate-induced lipid accumulation was inhibited in the presence of an ERα-selective antagonist, whereas it remained unaffected in the presence of a glucocorticoid receptor (GR)-specific inhibitor. In addition, fenvalerate was found to stimulate the expression of transcription factors that promote lipid accumulation in 3 T1-L1 adipocytes, and co-treatment with an ERα-selective antagonist suppressed adipogenic/ lipogenic transcription factors at both mRNA and protein levels. These findings suggest that fenvalerate exposure may lead to lipid accumulation by interfering with ERα activation-dependent processes, thus causing an ERα-mediated endocrine-disrupting effect. [Display omitted] • This study pointed out SHR-mediated endocrine disruption by fenvalerate. • Fenvalerate induced ERα-mediated endocrine disruption via a direct binding to ERα. • Fenvalerate did not induce on AR- and GR-mediated transcriptional activation activity. • Fenvalerate up-regulated the transcription level of lipid metabolism-related factors. • These adverse effect were by interfering with ERα activation-dependent processes. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) and its various forms used as BPA alternatives in industries are recognized toxic compounds and antiandrogenic endocrine disruptors. These chemicals are widespread in the environment and frequently detected in biological samples. Concerns exist about their impact on hormones, disrupting natural biological processes in humans, together with their negative impacts on the environment and biotic life. This study aims to characterize the interaction between BPA analogs and the androgen receptor (AR) and the effect on the receptor's normal activity. To achieve this goal, molecular docking was conducted with BPA and its analogs and dihydrotestosterone (DHT) as a reference ligand. Four BPA analogs exhibited higher affinity (−10.2 to −8.7 kcal/mol) for AR compared to BPA (−8.6 kcal/mol), displaying distinct interaction patterns. Interestingly, DHT (−11.0 kcal/mol) shared a binding pattern with BPA. ADMET analysis of the top 10 compounds, followed by molecular dynamics simulations, revealed toxicity and dynamic behavior. Experimental studies demonstrated that only BPA disrupts DHT-induced AR dimerization, thereby affecting AR's function due to its binding nature. This similarity to DHT was observed during computational analysis. These findings emphasize the importance of targeted strategies to mitigate BPA toxicity, offering crucial insights for interventions in human health and environmental well-being. [Display omitted] • BPA and its analogs are hazardous to animal, human, and environmental health. • The interaction of BPA and its analogs with AR in relation to DHT was studied. • The molecular interactions were confirmed both computationally and experimentally. • The binding of BPA and DHT was similar, while its analogs interacted differently. • Only BPA disrupts DHT-induced AR dimerization, impacting AR function. [ABSTRACT FROM AUTHOR]

Beauvericin (BEA) is a cyclic depsipeptide secondary metabolite of Fusarium species. It causes chemical hazards in food products and exists in an environment containing soil and various food types. On the other hand, the purified BEA has various biological activities and is regarded as a potential candidate for pharmaceutical research. This study was performed to assess the anti-proliferation activity of BEA against human breast cancer cells by regulating the estrogen receptor-alpha (ERα)/p38 pathway. TA and BA assays verified that BEA is a completed ER antagonist. Additionally, BEA suppressed cell proliferation in the anti-proliferation assay involving ER-positive human breast cancer cells co-treated with BPA and BEA. In respect to an anti-proliferation activity, the BPA-induced phosphorylation of p38 protein was inhibited in the presence of BEA. These results suggested that BEA exerts inhibitory potentials on endocrine disrupting effect and possibly acts as a natural therapeutic material for human estrogen hormonal health. [Display omitted] • BEA, a cyclic hexadepsipeptide was produced by Fusarium strain. • BEA has binding affinity to ERα, and suppressed homo-dimerization of ERαs in cytosol. • BEA determined to be an ERα antagonist in OECD PBTG No.455. • BEA suppressed the phosphorylation of p38 protein by exogenous estrogen. • This suppressing behavior caused the proliferation of ER-dependent breast cancer cells. [ABSTRACT FROM AUTHOR]

Fenhexamid are fungicides that act against plant pathogens by inhibiting sterol biosynthesis. Nonetheless, it can trigger endocrine disruption and promote breast cancer cell growth. In a recent study, we investigated the mechanism underlying the lipid accumulation induced by fenhexamid hydroxyanilide fungicides in 3 T3-L1 adipocytes. To examine the estrogen receptor alpha (ERα)-agonistic effect, ER transactivation assay using the ERα-HeLa-9903 cell line was applied, and fenhexamid-induced ERα agonist effect was confirmed. Further confirmation that ERα-dependent lipid accumulation occurred was provided by treating 3 T3-L1 adipocytes with Methyl-piperidino-pyrazole hydrate (MPP), an ERα-selective antagonist. Fenhexamid mimicked the actions of ERα agonists and impacted lipid metabolism, and its mechanism involves upregulation of the expression of transcription factors that facilitate adipogenesis and lipogenesis. Additionally, it stimulated the expression of peroxisome proliferator-activated receptor (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1 (SREBP1) and significantly elevated the expression of fatty acid-binding protein 4 (FABP4). In contrast, in combination with an ERα-selective antagonist, fenhexamid suppressed the expression of adipogenic/lipogenic transcription factors. These results suggest that fenhexamid affects the endocrine system and leads to lipid accumulation by interfering with processes influenced by ERα activation. [Display omitted] • This study revealed the lipid accumulation mechanism of fungicide, fenhexamid. • Fenhexamid is classified to an ERα agonist in hERα-HeLa-9903 ERTA assay. • ERα agonistic effect induced by fenhexamid decrease in the presence of phase I + II enzymes. • Fenhexamid treatment induces ERα-dependent lipid accumulation in in 3 T3-L1 adipocytes. • Fenhexamid shows ERα-dependent regulating adipogenetic/lipogenetic transcription factors. [ABSTRACT FROM AUTHOR]

Trenbolone acetate (TBA) is a synthetic anabolic steroidal growth factor that is used for rapid muscle development in cattle. The absorbed TBA is hydrolyzed to the active form, 17β-trenbolone (17 TB; 17β-hydroxy-estra-4,9,11-trien-3-one) in meat and milk products, which can cause adverse health effects in humans. Similar to 5α-dihydrotestosterone (DHT), 17 TB was reported to exhibit endocrine disrupting effects on animals and humans due to its androgenic effect via binding to the androgen receptor. The purpose of this study is to investigate the molecular mechanism of cell proliferation in prostate cancer (PCa) cells treated with 17 TB. We found that 17 TB induces AR-dependent cell proliferation in the human prostate cancer cell line, 22Rv1 in a concentration dependent manner. Treatment with 17 TB increased the expression of cell cycle regulatory proteins, cyclin D2/CDK-4 and cyclin E/CDK-2, whereas the expression of p27 was down-regulated. Furthermore, phosphorylation of Rb and activation of E2F were also induced, which suggests the activation of cyclin D2/CDK-4 and cyclin E/CDK-2 in the cells. When 22Rv1 cells were exposed to 30 pM of 17 TB, which is the effective concentration (EC 50 ) value required to observe proliferative effects on 22Rv1 cells, the expression levels of the phosphorylated forms of Akt and GSK3β were increased. This study demonstrates that 17 TB induces AR-dependent proliferation through the modulation of cell cycle-related proteins in the Akt signaling pathway. The present study provides an effective methodology for identifying cell proliferation signaling of veterinary drugs that exert AR agonistic effects. [ABSTRACT FROM AUTHOR]

Objective: Nocturnal pulse oximetry has been proposed as a simpler alternative to polysomnography in diagnosing sleep apnea. However, existing techniques are limited in terms of inability to provide time information on sleep apnea occurrence. This study aimed to propose a new strategy for near real-time automatic detection of apneic events and reliable estimation of apnea–hypopnea index using nocturnal pulse oximetry. Methods: Among 230 polysomnographic recordings with apnea–hypopnea index values ranging from 0 to 86.5 events/h, 138 (60%) and the remaining 92 recordings (40%) were categorized as training and test sets, respectively. By extracting the quantitative characteristics caused by the apneic event for the amount and duration of the change in blood oxygen saturation value, we established the criteria to determine the occurrence of apneic event. Regression modeling was used to estimate the apnea–hypopnea index from the apneic event detection results. Results: The minute-by-minute apneic segment detection exhibited an average accuracy of 91.0% and an average Cohen's kappa coefficient of 0.71. Between the apnea–hypopnea index estimations and reference values, the mean absolute error was 2.30 events/h. The average accuracy of our diagnosis of sleep apnea was 96.7% for apnea–hypopnea index cutoff values of ≥5, 10, 15, and 30 events/h. Conclusion: We developed an effective strategy to detect apneic events by using morphometric characteristics in the fluctuation of blood oxygen saturation values. Significance: Our study could be potentially useful in home-based multinight apneic event monitoring for purposes of therapeutic intervention and follow-up study on sleep apnea. [ABSTRACT FROM PUBLISHER]

publisher‐imprint‐name Springer volume‐issue‐count 1 issue‐article‐count 0 issue‐toc‐levels 0 issue‐pricelist‐year 2017 issue‐copyright‐holder The Author(s) issue‐copyright‐year 2017 article‐contains‐esm No article‐numbering‐style Unnumbered article‐registration‐date‐year 2017 article‐registration‐date‐month 3 article‐registration‐date‐day 11 article‐toc‐levels 0 toc‐levels 0 volume‐type Regular journal‐product ArchiveJournal numbering‐style Unnumbered article‐grants‐type OpenChoice metadata‐grant OpenAccess abstract‐grant OpenAccess bodypdf‐grant OpenAccess bodyhtml‐grant OpenAccess bibliography‐grant OpenAccess esm‐grant OpenAccess online‐first false pdf‐file‐reference BodyRef/PDF/40169_2017_Article_143.pdf target‐type OnlinePDF issue‐type Regular article‐type Letter journal‐subject‐primary Medicine & Public Health journal‐subject‐secondary Medicine/Public Health, general journal‐subject‐collection SC11 --> The ability of salamanders, such as newts, to regenerate damaged tissues has been studied for centuries. A prominent example of this regenerative power is the ability to re‐grow entire amputated limbs. One important step in this regeneration process is skeletal muscle cellularization, in which the muscle fibers break down into dedifferentiated, mononuclear cells that proliferate and form new muscle in the replacement limb. In contrast, mammalian skeletal muscle does not undergo cellularization after injury. A significant proportion of research about tissue regeneration in salamanders aims to characterize regulatory genes that may have mammalian homologs. A less mainstream approach is to develop small molecule compounds that induce regeneration‐related mechanisms in mammals. In this commentary, we discuss progress in discovering small molecules that induce cellularization in mammalian muscle. New research findings using these compounds has also shed light on cellular processes that regulate cellularization, such as apoptotic signaling. Although formidable technical hurdles remain, this progress increases our understanding of tissue regeneration and provide opportunities for developing small molecules that may enhance tissue repair in humans. [ABSTRACT FROM AUTHOR]

We assessed the mechanism of human androgen receptor-mediated endocrine-disrupting effect by a triazole fungicide, metconazole in this study. The internationally validated stably transfected transactivation (STTA) in vitro assay, which was established for determination of a human androgen receptor (AR) agonist/antagonist by using 22Rv1/MMTV_GR-KO cell line, alongside an in vitro reporter-gene assay to confirm AR homodimerization was used. The STTA in vitro assay results showed that metconazole is a true AR antagonist. Furthermore, the results from the in vitro reporter-gene assay and western blotting showed that metconazole blocks the nuclear transfer of cytoplasmic AR proteins by suppressing the homodimerization of AR. These results suggest that metconazole can be considered to have an AR-mediated endocrine-disrupting effect. Additionally, the evidence from this study might help identify the endocrine-disrupting mechanism of triazole fungicides containing a phenyl ring. [Display omitted] • Metconazole has endocrine-disrupting effect. • Metconazole was determined as an AR antagonist in transcriptional activation assay. • Metconazole inhibited the dimerization of AR in cytoplasm. • The 'dimerization' inhibition causes to block the nuclear translocation of cytoplasmic AR proteins. • AR antagonistic effect is caused by inhibiting the dimerization of ligand-bound ARs in cytoplasm. [ABSTRACT FROM AUTHOR]

The ability of salamanders, such as newts, to regenerate damaged tissues has been studied for centuries. A prominent example of this regenerative power is the ability to re-grow entire amputated limbs. One important step in this regeneration process is skeletal muscle cellularization, in which the muscle fibers break down into dedifferentiated, mononuclear cells that proliferate and form new muscle in the replacement limb. In contrast, mammalian skeletal muscle does not undergo cellularization after injury. A significant proportion of research about tissue regeneration in salamanders aims to characterize regulatory genes that may have mammalian homologs. A less mainstream approach is to develop small molecule compounds that induce regeneration-related mechanisms in mammals. In this commentary, we discuss progress in discovering small molecules that induce cellularization in mammalian muscle. New research findings using these compounds has also shed light on cellular processes that regulate cellularization, such as apoptotic signaling. Although formidable technical hurdles remain, this progress increases our understanding of tissue regeneration and provide opportunities for developing small molecules that may enhance tissue repair in humans. [ABSTRACT FROM AUTHOR]

Sleep efficiency is a commonly and widely used measure to objectively evaluate sleep quality. Monitoring sleep efficiency can provide significant information about health conditions. As an attempt to facilitate less cumbersome monitoring of sleep efficiency, our study aimed to suggest new predictors of sleep efficiency that enable reliable and unconstrained estimation of sleep efficiency during awake resting period. We hypothesized that the autonomic nervous system activity observed before falling asleep might be associated with sleep efficiency. To assess autonomic activity, heart rate variability and breathing parameters were analyzed for 5 min. Using the extracted parameters as explanatory variables, stepwise multiple linear regression analyses andk-fold cross-validation tests were performed with 240 electrocardiographic and thoracic volume change signal recordings to develop the sleep efficiency prediction model. The developed model’s sleep efficiency predictability was evaluated using 60 piezoelectric sensor signal recordings. The regression model, established using the ratio of the power of the low- and high-frequency bands of the heart rate variability signal and the average peak inspiratory flow value, provided an absolute error (mean ± SD) of 2.18% ± 1.61% and a Pearson’s correlation coefficient of 0.94 (p< 0.01) between the sleep efficiency predictive values and the reference values. Our study is the first to achieve reliable and unconstrained prediction of sleep efficiency without overnight recording. This method has the potential to be utilized for home-based, long-term monitoring of sleep efficiency and to support reasonable decision-making regarding the execution of sleep efficiency improvement strategies. [ABSTRACT FROM AUTHOR]

With the high prevalence of obstructive sleep apnea, the issue of developing a practical tool for obstructive sleep apnea screening has been raised. Conventional obstructive sleep apnea screening tools are limited in their ability to help clinicians make rational decisions due to their inability to predict the apnea-hypopnea index. Our study aimed to develop a new prediction model that can provide a reliable apnea-hypopnea index value during wakefulness. We hypothesized that patients with more severe obstructive sleep apnea would exhibit more attenuated waking vagal tone, which may result in lower effectiveness in decreasing heart rate as a response to deep inspiration breath-holding. Prior to conducting nocturnal in-laboratory polysomnography, 30 non-obstructive sleep apnea (apnea-hypopnea index < 5 events/h) subjects and 246 patients with obstructive sleep apnea participated in a 75-second experiment that consisted of a 60-second baseline measurement and consecutive 15-second deep inspiration breath-hold sessions. Two apnea-hypopnea index predictors were devised by considering the vagal activities reflected in the electrocardiographic recordings acquired during the experiment. Using the predictors obtained from 184 individuals, regression analyses and k -fold cross-validation tests were performed to develop an apnea-hypopnea index prediction model. For the remaining 92 individuals, the developed model provided an absolute error (mean ± SD) of 3.53 ± 2.67 events/h and a Pearson's correlation coefficient of 0.99 ( P < 0.01) between the apnea-hypopnea index predictive values and the reference values reported by polysomnography. Our study is the first to achieve reliable and time-efficient prediction of the apnea-hypopnea index during wakefulness. [ABSTRACT FROM AUTHOR]

The most widely used methods for predicting obstructive sleep apnea are based on clinical or anatomico-functional features. To improve exactitude in obstructive sleep apnea screening, this study aimed to devise a new predictor of apnea–hypopnea index. We hypothesized that less irregular respiration cycles would be observed in the patients with more severe obstructive sleep apnea during the sleep-onset period. From each of the 156 and 70 single-lead electrocardiograms collected from the internal polysomnographic database and from the Physionet Apnea-ECG database, respectively, the 150-s sleep-onset period was determined and the respiration cycles during this period were detected. Using the coefficient of variation of the respiration cycles, obtained from the internal dataset, as a predictor, the apnea–hypopnea index predictive model was developed through regression analyses and k-fold cross-validations. The apnea–hypopnea index predictability of the regression model was tested with the Physionet Apnea-ECG database. The regression model trained and validated from the 143 and 13 data, respectively, produced an absolute error (mean ± SD) of $3.65 \pm 2.98$ events/h and a Pearson's correlation coefficient of 0.97 (P < 0.01) between the apnea–hypopnea index predictive values and the reference values for the 70 test data. The new predictor of apnea–hypopnea index has the potential to be utilized in making more reasoned clinical decisions on the need for formal diagnosis and treatment of obstructive sleep apnea. Our study is the first study that presented the strategy for providing a reliable apnea–hypopnea index without overnight recording. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether fermented Platycodon grandiflorum (FPG) inhibits lipid accumulation in 3T3-L1 adipocytes and mice with high-fat diet (HFD)-induced obesity. We evaluated the effect of FPG on antiadipogenic activity via regulation of peroxisome proliferator-activated receptor gamma (PPAR γ) and CCAAT/enhancer-binding protein alpha (C/EBP α), as well as protein expression of their target genes, fatty acid binding protein 4 (FABP4). We further examined the antiobesity effects of FPG on HFD-induced obesity in mice. The FPG was orally administered to mice with a HFD at 50, 100, or 200 mg/kg/day for 8 weeks. Our results show that FPG significantly inhibited fat accumulation during 3T3-L1 adipogenesis through downregulating adipogenic transcript factors. Moreover, FPG markedly reduced the final body weight with a decrease in epididymal adipose tissue mass and adipocyte size compared with the untreated HFD-induced group. The effects of FPG on HFD-induced obesity were primarily responsible for inhibiting adipogenesis in adipose tissue and regulating lipid metabolism, such as through lipogenesis and fatty acid oxidation. Additionally, FPG ameliorated serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Hence, FPG may be an alternative treatment for controlling obesity through downregulating lipid accumulation. [ABSTRACT FROM AUTHOR]

Background: Nocturnal hypoxemia, characterized by abnormally low oxygen saturation levels in arterial blood during sleep, is a significant feature of various pathological conditions. The oxygen desaturation index, commonly used to evaluate the nocturnal hypoxemia severity, is acquired using nocturnal pulse oximetry that requires the overnight wear of a pulse oximeter probe. Objectives: This study aimed to suggest a method for the unconstrained estimation of the oxygen desaturation index. Methods: We hypothesized that the severity of nocturnal hypoxemia would be positively associated with cardiac sympathetic activation during sleep. Unconstrained heart rate variability monitoring was conducted using three different ballistocardio- graphic systems to assess cardiac sympathetic activity. Overnight polysomnographic and ballistocardiographic recording pairs were collected from the 20 non-nocturnal hypoxemia (oxygen desaturation index <5 events/h) subjects and the 76 nocturnal hypoxemia patients. Among the 96 recording pairs, 48 were used as training data and the remaining 48 as test data. Results: The regression analysis, performed using the low-frequency component of heart rate variability, exhibited a root mean square error of 3.33 events/h between the estimates and the reference values of the oxygen desaturation index. The nocturnal hypoxemia diagnostic performance produced by our method was presented with an average accuracy of 96.5% at oxygen desaturation index cutoffs of ⩾ 5, 15, and 30 events/h. Conclusions: Our method has the potential to serve as a complementary measure against the accidental slip-out of a pulse oximeter probe during nocturnal pulse oximetry. The independent application of our method could facilitate homebased long-term oxygen desaturation index monitoring. [ABSTRACT FROM AUTHOR]

Summary Glycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic “moonlighting” functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes. [ABSTRACT FROM AUTHOR]

The study of symmetric rings has important roles in ring theory and module theory. We investigate the structure of ring properties related to symmetric rings and introduce H-symmetric and π-symmetric as generalizations. We construct a non-symmetric reversible ring whose basic structure is infinite-dimensional, comparing with the finite-dimensional such rings of Anderson, Camillo and Marks. The structure of π-reversible rings (with or without identity) of minimal order is completely investigated. The properties of zero-dividing polynomials over IFP rings are studied more to show that polynomial rings over symmetric rings are π-symmetric. It is also proved that all conditions in relation with our arguments in this paper are equivalent for regular or locally finite rings. [ABSTRACT FROM AUTHOR]

Fragmented sleep due to frequent awakenings represents a major cause of impaired daytime performance and adverse health outcomes. Currently, the gold standard for studying and assessing sleep fragmentation is polysomnography (PSG). Here, we propose an alternative method for real-time detection of nocturnal awakening via ballistocardiography using an unobtrusive polyvinylidene fluoride (PVDF) film sensor on a bed mattress. From ballistocardiogram, heart rate and body movement information were extracted to develop an algorithm for classifying sleeping and awakening epochs. In total, ten normal subjects (mean age 38.7 ± 14.6 years) and ten patients with obstructive sleep apnea (OSA) (mean age 44.2 ± 16.5 years) of varying symptom severity participated in this study. Our study detected awakening epochs with an average sensitivity of 85.3% and 85.2%, specificity of 98.4% and 97.7%, accuracy of 97.4% and 96.5%, and Cohen's kappa coefficient of 0.83 and 0.81 for normal subjects and OSA patients, respectively. Also, sleep efficiency was estimated using detected awakening epochs and then compared with PSG results. Mean absolute errors in sleep efficiency were 1.08% and 1.44% for normal subjects and OSA patients, respectively. The results presented here indicate that our suggested method could be reliably applied to real-time nocturnal awakening detection and sleep efficiency estimation. Furthermore, our method may ultimately be an effective tool for long-term, home monitoring of sleep–wake behavior. [ABSTRACT FROM PUBLISHER]

We continue the study of nil-Armendariz rings, initiated by Antoine, and Armendariz rings. We first examine a kind of ring coproduct constructed by Antoine for which the Armendariz, nil-Armendariz, and weak Armendariz properties are equivalent. Such a ring has an important role in the study of Armendariz ring property and near-related ring properties. We next prove an Antoine's result in relation with the ring coproduct by means of a simpler direct method. In the proof we can observe the concrete shapes of coefficients of zero-dividing polynomials. We next observe the structure of nil-Armendariz rings via the upper nilradicals. It is also shown that a ring R is Armendariz if and only if R is nil-Armendariz if and only if R is weak Armendariz, when R is a von Neumann regular ring. [ABSTRACT FROM AUTHOR]

Summary: Carcinoma-associated fibroblasts (CAFs) promote tumor invasion by secreting soluble factors. A tagged triazine library was screened in our novel transwell coculture model of CAF and oral squamous cell carcinoma (OSCC). We discovered compound S06, which reduced OSCC invasion by inhibiting secretion of CAF-derived proinvasive chemokines. The N-terminus of Hsp90 was found to be the cellular target of S06. Importantly, S06 did not induce hepatic toxicity, a side effect associated with well-known Hsp90 inhibitors. Moreover, S06 inhibited tumor cell migration in a zebrafish xenograft model. Our results demonstrate that Hsp90 is a novel target for stromal-based therapy to modulate proinvasive molecular crosstalk within the tumor microenvironment. Furthermore, S06 represents a new class of Hsp90 inhibitor and is an attractive candidate for anticancer drug development. [ABSTRACT FROM AUTHOR]

Abstract: Nano-sized antimony-doped tin oxide (ATO) particles were synthesized using DC arc plasma jet. The precursors SnCl4 and SbCl5 were injected into the plasma flame in the vapor phase. ATO powder could conveniently be synthesized without any other post-treatment in this study. To control the doping amount of antimony in the ATO particles, the Sb/Sn molar ratio was used as an operating variable. To study the effect of carrier gas on the particle size, argon and oxygen gases were used. The results of XRD and TGA show that all Sb ions penetrated the SnO2 lattice to substitute Sn ions. With the increased SbCl5 concentration in source material, the Sb doping level was also increased. The size of the particles synthesized using the argon carrier gas was much smaller than that of the particles prepared using the oxygen carrier gas. For the argon gas, PSA results and SEM images reveal that the average particle size was 19nm. However, for the oxygen gas, the average particle size was 31nm. [Copyright &y& Elsevier]

A triazine-based combinatorial library of small molecules was screened in albino murine melanocytes to identify compounds that induce pigmentation. Six compounds (of 1536 screened) produced at least 3-fold increases in pigmentation. Immunohistochemical studies demonstrated that the compounds conferred correct routing of the mistrafficked enzyme tyrosinase, which is critical to normal melanogenesis. Affinity matrices of the immobilized compounds allowed the cellular target to be identified as the mitochondrial F1F0-ATP synthase. Oligomycin and aurovertin B, small molecules known to inhibit the mitochondrial ATP synthase, were shown to compete with the triazine-based compounds for their cellular target in albino melanocytes and confer similar effects on pigmentation and tyrosinase rerouting. This is the first demonstration of the mitochondrial ATP synthase as a potential therapeutic target for restoring pigmentation in albino melanocytes. [Copyright &y& Elsevier]

A highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) method has been developed for the determination of 20(S)-protopanaxatriol (PPT), one of the major aglycones of dammarane-type ginseng saponins. Polyclonal antibodies raised against ginsenoside F1 (GF1)-bovine serum albumin showed high reactivities to PPT and GF1, whereas they exhibited minor or even no cross-reactivities to other ginsenosides and protopanaxadiol (0.19%). The working range of this method extends from 50 pg ml−1 to 20 ng ml−1 of PPT. The assay reported here has been validated against an HPLC technique using PPT-containing samples and was shown to correlate closely (γ=0.993). This ELISA could be a useful tool for the determination of PPT contained in biological fluids and plant materials. [Copyright &y& Elsevier]

We describe the characterisation and validation of an androgen receptor (AR) transactivation assay for detection of AR agonists and antagonists using a stably transfected human prostate cancer cell line. This 22Rv1/mouse mammary tumour virus glucocorticoid knock-out cell line based AR transactivation assay was validated by criteria in Organisation for Economic Cooperation and Development Guidance Document 34 to determine if the assay performed equally well to the AR EcoScreen Assay included in Test Guideline for AR Transactivation (OECD TG 458). There was no Glucocorticoid Receptor (GR) crosstalk, and no changes in the AR DNA sequence in cells after the successful knock out of GR. Subsequently, the concordance of classifications of the 22 test chemicals was 100% in all laboratories. The AR agonistic and antagonistic inter-laboratory coefficients of variation based on log[10% effect for 10 nM DHT, PC 10 ] and log[inhibitory response of 800 pM DHT by at 30%, IC 30 ] from comprehensive tests were 2.75% and 2.44%, respectively. The AR agonist/antagonist test chemical classifications were consistent across AR EcoScreen ARTA assay data for 82/89%, and the balanced accuracy, sensitivity, and specificity were 83/90%, 88/100% and 78/80%, respectively. This assay was successfully validated and was approved for inclusion in TG 458 in 2020. • The characterisation and validation of a TA assay to detect AR agonists/antagonists was completed. • This assay was established using stably transfected a 22Rv1/MMTV GR knock-out cell line. • It was confirmed that there was no GR crosstalk, and no changes in the AR sequence in cells. • The validation study met the required criteria as described in OECD TG 458. • This test method was approved for inclusion in OECD TG 458 in 2020. [ABSTRACT FROM AUTHOR]

Targeted therapies for inhibiting the growth of cancer cells or inducing apoptosis are urgently needed for effective rhabdomyosarcoma (RMS) treatment. However, identifying cancer-targeting compounds with few side effects, among the many potential compounds, is expensive and time-consuming. A computational approach to reduce the number of potential candidate drugs can facilitate the discovery of attractive lead compounds. To address this and obtain reliable predictions of novel cell-line-specific drugs, we apply prediction models that have the potential to improve drug discovery approaches for RMS treatment. The results of two prediction models were ensemble and validated via in vitro experiments. The computational models were trained using data extracted from the Genomics of Drug Sensitivity in Cancer database and tested on two RMS cell lines to select potential RMS drug candidates. Among 235 candidate drugs, 22 were selected following the result of the computational approach, and three candidate drugs were identified (NSC207895, vorinostat, and belinostat) that showed selective effectiveness in RMS cell lines in vitro via the induction of apoptosis. Our in vitro experiments have demonstrated that our proposed methods can effectively identify and repurpose drugs for treating RMS. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts(CAFs) participate in carcinogenesis through interaction with cancer cells. This study aimed to investigate the mechanism of cytoskeletal alteration of CAFs and its role in invasion of oral squamous cell carcinoma(OSCC).Immortalized normal fibroblasts(hTERT-hNOFs) co-cultured with OSCC cells showed myofibroblastic and senescent phenotypes like CAFs. Thus, this study substituted hTERT-hNOFs for CAFs. Next, the cytoskeletal alteration and its molecular mechanism were investigated in hTERT-hNOFs co-cultured with OSCC. As results, we found that RhoA regulated cytoskeletal organization in fibroblasts surrounding OSCC cells. Furthermore, as a downstream transcriptional factor of RhoA, YAP was mainly localized in the nucleus of hTERT-hNOFs co-cultured with OSCC. Consequently, we examined whether nuclear YAP localization of fibroblasts could influence cancer progression. YAPS127A fibroblasts manifesting nuclear localization of YAP induced cytoskeletal alteration and increased gel contractility and matrix stiffness, and thereby enhances the invasiveness of OSCC cells. In conclusion, the modification of tumor microenvironment, such as cytoskeletal change and matrix remodeling via RhoA-YAP in CAFs, modulates OSCC invasion. These understandings will provide the development of novel approaches for CAFs-based cancer therapy. [ABSTRACT FROM AUTHOR]

This paper, concerns a class of rings which satisfies the Abelian property in relation to the insertion property at zero by powers and local finite. The concepts of Insertion of-Power-Factors-Property (PFP) and principal finite are introduced for the purpose, and the structures of IPFP, Abelian and locally (principally) finite rings are investigated in relation with several situations of matrix rings and polynomial rings. Moreover, the results obtained here are widely applied to various sorts of rings which have roles in the noncommutative ring theory. [ABSTRACT FROM AUTHOR]

As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Ca v 3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Ca v 3.2 currents (>90% inhibition) at 10 μM concentration and exhibited cytotoxic effect (IC 50 = 5.9 μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S. Furthermore, 8h showed approximately a 2-fold increase in liver metabolic stability in rat and human species compared to KYS05090S. Based on these overall results, 8h (KCP10068F) may therefore represent a good backup compound for KYS05090S for further biological investigations as novel cytotoxic agent. In addition, compound 8g (KCP10067F) was found to partially protect from inflammatory pain via a blockade of Ca v 3.2 channels. [ABSTRACT FROM AUTHOR]

Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential “hits” fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a “bridge” to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories. [ABSTRACT FROM AUTHOR]

In this study, we investigated the anti-diabetic effect of Aster sphathulifolius (AS) extract in C57BL/KsJ- db/db mice. The db/db mice were orally administered with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day ( db/ db-AS50, db/ db-AS100, and db/ db-AS200, respectively) for 10 weeks. Food and water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the db/ db-AS200 group than in the vehicle-treated db/ db group; whereas glucose tolerance was significantly improved in the db/ db-AS200 group. Moreover, AS dose dependently increased both insulin receptor substrate 1 and glucose transporter type 4 expression in skeletal muscle, significantly increased glucokinase expression, and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase expressions in the liver. The expressions of transcription factors, such as sterol-regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and adipocyte protein 2, were upregulated in adipose tissue. Furthermore, immunohistochemical analysis showed that AS upregulated insulin production by increasing pancreatic β-cell mass. In summary, AS extract normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis, acceleration of glucose metabolism and lipid metabolism, and increase of glucose uptake. Using in vivo assays, this study has shown the potential of AS as a medicinal food and suggests the efficacy of AS for the use of prevention of diabetes. [ABSTRACT FROM AUTHOR]

The single-file root canal instrumentation technique using reciprocating motion has been gaining concern. Therefore, the purpose of this study was to compare the shaping ability of single Pro Taper F2 file and Wave One Primary file when they were used in the curved root canal with reciprocation motion and to investigate the durability of the file after use with a scanning electron microscopy ( SEM). Changes in structure model index ( SMI), root canal volume, curvature, surface area, and degree of transportation were measured from the cross-sectional images of the prepared canals using the micro- CT system with an isotropic resolution of 16 μm. Results showed that there were no differences in the changes of root canal volume, surface area, and SMI between the two file groups after the preparation ( p > 0.05). The Pro Taper group showed a curvature straightening value of 25.45 ± 12.51%, while the Wave One group showed 27.30 ± 10.91%, and there was no statistically significant difference ( p > 0.05). The transportation values between the two groups showed no significant differences ( p > 0.05). SEM revealed that 60% of Pro Taper files showed initiation of microcracks on the surface while those were detected on the only one Wave One file. The single-file technique using either Wave One Primary or Pro Taper F2 can be safely used under each reciprocating motion without creating an increased apical transportation in curved canals. However, the metallurgic property resists cyclic fatigue was more favorable with Wave One under the scanning evaluation. SCANNING 35: 112-118, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Glucose homeostasis is a fundamental aspect of life and its dysregulation is associated with important diseases, such as cancer and diabetes. Traditionally, glucose radioisotopes have been used to monitor glucose utilization in biological systems. Fluorescent-tagged glucose analogues were initially developed in the 1980s, but it is only in the past decade that their use as a glucose sensor has increased significantly. These analogues were developed for monitoring glucose uptake in blood cells, but their recent applications include tracking glucose uptake by tumor cells and imaging brain cell metabolism. This review outlines the development of fluorescent-tagged glucose analogues, describes their recent structural modifications and discusses their increasingly diverse biological applications. [ABSTRACT FROM AUTHOR]

Background. There are few studies focused on bronchial challenge testing using the oscillation technique, and results from the test in preschool children have been inconsistent. Objectives. The aim of this study was to explore which level of provocative concentration (PC) is appropriate for bronchial challenge testing using the impulse oscillometry system (IOS) for assessing asthma. The authors also compared variable diagnostic cutoff values of PC expressed in different ways.  Methods. A methacholine challenge test was performed using an IOS and the mean baseline value, resistance (Rrs), reactance (Xrs), resonance frequency (Rf), and area of reactance (AX) of the respiratory system were recorded simultaneously over a frequency spectrum of 5 to 35 Hz in 50 preschool children with asthma and 41 children with chronic cough, serving as controls. Results. The results of the methacholine challenge test by IOS, expressed as percent changes of the predicted value (Δ%Pred), were significantly different between the two groups, whereas results expressed as actual data or Z-score were not. PC80_Xrs5 was a valuable diagnostic cutoff level for asthma with acceptable sensitivity (80.0%) and specificity (82.9%). The areas under the ROC curves of Xrs5 for both actual (0.867; p < .001) and predicted values (0.877; p < .001) were larger than those for Rrs5 (0.746 and 0.730, respectively). Conclusions. The authors suggest PC80_Xrs5 might be a useful parameter for IOS-assessed bronchial challenge testing in preschool children with asthma. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle. [ABSTRACT FROM AUTHOR]

Aging is associated with increased prevalence of skeletal and cardiac muscle disorders, such as sarcopenia and cardiac infarction. In this study, we constructed a compendium of purified ginsenoside compounds from Panax ginseng C.A. Meyer, which is a traditional Korean medicinal plant used to treat for muscle weakness. Skeletal muscle progenitor cell-based screening identified three compounds that enhance cell viability, of which 20(R)-ginsenoside Rh2 showed the most robust response. 20(R)-ginsenoside Rh2 increased viability in myoblasts and cardiomyocytes, but not fibroblasts or disease-related cells. The cellular mechanism was identified as downregulation of cyclin-dependent kinase inhibitor 1B (p27Kip1) via upregulation of Akt1/PKB phosphorylation at serine 473, with the orientation of the 20 carbon epimer being crucially important for biological activity. In zebrafish and mammalian models, 20(R)-ginsenoside Rh2 enhanced muscle cell proliferation and accelerated recovery from degeneration. Thus, we have identified 20(R)-ginsenoside Rh2 as a p27Kip1 inhibitor that may be developed as a natural therapeutic for muscle degeneration. [ABSTRACT FROM AUTHOR]

The presence of veterinary drug residues in foods and the environment could potentially cause adverse effects on humans and wildlife. Several veterinary drugs were reported to exhibit endocrine disrupting effects via binding affinities to sexual hormone receptors such as estrogen and androgen receptors. Therefore, we confirmed the human estrogen receptor (ER) agonistic/antagonistic effects of 135 chemicals that were used as veterinary drugs in Korea by the official Organization for Economic Cooperation and Development (OECD) in vitro ER transcriptional activation (TA) assay using the VM7Luc4E2 cell line. In the case of ER agonist screening, 7 veterinary drugs (cefuroxime, cymiazole, trenbolone, zeranol, phoxim, altrenogest and nandrolone) were determined to be ER agonists. In addition, only zeranol was found to exhibit weak ER antagonistic activity. These 7 veterinary drugs, which were determined as ER agonists and/or antagonists by an OECD in vitro assay, were also found to have binding affinity to ERs. These results indicate that various veterinary drugs possess potential (anti-)estrogenic effects. However, further study is needed to determine the precise endocrine-disrupting effects of these compounds. • ER agonistic/antagonistic effects of 135 veterinary drugs, used in Korea, are assessed. • OECD in vitro stably transfected transcriptional activation assays using the VM7Luc4E2 cell line are applied. • Cefuroxime, cymiazole, trenbolone, zeranol, phoxim, altrenogest and nandrolone) are determined to be ER agonists. • Zenarol also exhibited a weak ER antagonistic effect. • This report provides valuable evidences about potential endocrine disrupting effects of various veterinary drugs. [ABSTRACT FROM AUTHOR]

Indirubin-based compounds affect diverse biological processes, such as inflammation and angiogenesis. In this study, we tested a novel indirubin derivative, LDD-1819 (2-((((2Z,3E)-5-hydroxy-5′-nitro-2′-oxo-[2,3′-biindolinylidene]-3-ylidene)amino)oxy)ethan-1-aminium chloride) for two major biological activities: cell plasticity and anti-cancer activity. Biological assays indicated that LDD-1819 induced somatic cell plasticity. LDD-1819 potentiated myoblast reprogramming into osteogenic cells and fibroblast reprogramming into adipogenic cells. Interestingly, in an assay of skeletal muscle dedifferentiation, LDD-1819 induced human muscle cellularization and blocked residual proliferative activity to produce a population of mononuclear refractory cells, which is also observed in the early stages of limb regeneration in urodele amphibians. In cancer cell lines, LDD-1819 treatment inhibited cell invasion and selectively induced apoptosis compared to normal cells. In an animal tumor xenograft model, LDD-1819 reduced human cancer cell metastasis in vivo at doses that did not produce toxicity. Biochemical assays showed that LDD-1819 possessed inhibitory activity against glycogen synthase kinase-3β, which is linked to cell plasticity, and aurora kinase, which regulates carcinogenesis. These results indicate that novel indirubin derivative LDD-1819 is a dual inhibitor of glycogen synthase kinase-3β and aurora A kinase, and has potential for development as an anti-cancer drug or as a reprogramming agent for cell-therapy based approaches to treat degenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Recurrent laryngeal nerve (RLN) palsy is a serious complication of thyroid surgery. During intraoperative neuromonitoring (IONM) of the RLN in thyroid surgery, repeated shifting between surgical instruments and the nerve stimulator is cumbersome and time-consuming. Therefore, we developed a simple detachable magnetic nerve stimulator that may be connected to all metallic surgical instruments. This study aimed to investigate the feasibility and efficacy of this detachable magnetic nerve stimulator for IONM in a porcine model and humans. Methods: Eight RLNs in four pigs and thirteen in nine patients that underwent thyroidectomy were examined. We developed a detachable nerve stimulator that combined surgical instruments with the nerve-stimulating probe. We evaluated the electromyography (EMG) amplitudes of the RLNs in pigs and patients using conventional nerve probes and surgical instruments with the novel detachable magnetic nerve stimulator attached. Results: The EMG amplitudes of the eight RLNs in pigs and thirteen in patients were analyzed. The detachable magnetic nerve stimulator was feasible and safe. There was no significant difference in the EMG amplitude between instruments ( P = 0.423 in animals, P = 0.446 in humans). Conclusions: The application of stimulating dissection using a detachable magnetic nerve stimulator during thyroidectomy with IONM is simple, convenient, and effective. It provides surgeons with real-time feedback of the EMG response during intermittent IONM. We propose that this novel device could be an essential guide for most surgeons, especially for less experienced head and neck surgeons. [ABSTRACT FROM AUTHOR]

For the next generation display devices, dry etching technique for indium tin oxide (ITO) used as a transparent electrode is required to obtain a highly anisotropic etch profile, and to decrease the dimensional loss after the etching. For the dry etching of ITO, the easy dry cleaning of etch byproducts attached to the chamber wall during the dry etching is also important. In this study, by using novel hydrocarbon gases mixed with Ar, such as ethane (C 2 H 6) and propane (C 3 H 8), the dry etch characteristics and the etch residue cleaning process have been investigated using an inductively coupled plasma etcher, and the results were compared with the conventionally investigated methane (CH 4)-based gases, such as CH 4 and CH 4 /H 2 mixed with Ar. The result showed that the hydrogen in CH 4 /H 2 both decreased the ITO etch rate, and decreased the etch selectivity over photoresist (PR). By using hydrogen-less hydrocarbon gas having the alkane structure, such as C x H 2x+2 (x = 2, 3), both the ITO etch rate and the etch selectivity were increased with the increase of carbon in the alkane structure; therefore, the highest etch rate was observed for C 3 H 8. In addition, with the increase of x in the carbon of C x H 2x+2 , less dimensional loss, more anisotropic etch profile, and lower surface roughness could be observed. During the etching, etch residues containing C, In, Sn, O, and H were accumulated on the chamber wall due to the low volatility of the etch byproducts; however, the etch residues formed by all three hydrocarbon gases could be successfully dry cleaned using H 2 /Ar plasmas through the formation of InC x H y (x < y), CO x , and S n H x. • Etching of ITO with H 2 /CH 4 showed damage on the photoresist surface due to the redeposition of etch byproduct on the photoresist (PR) surface while etching the PR with hydrogen. • In C x H 2x+2 (x = 1,2,3)/Ar, the etch rate of ITO and the etch selectivity over PR increased as x is increased in the order of CH 4 , C 2 H 6 , and C 3 H 8 while showing no damage to the PR surface. • Due to the increase of etch selectivity, more anisotropic etch profile angle was observed in the order of CH 4 , C 2 H 6 , and C 3 H 8. • The residue was deposited on the chamber wall during the etching of ITO using C x H 2x+2 (x = 1,2,3)/Ar, however, the residue on the chamber wall could be completely cleaned by a H 2 /Ar plasma generated by the ICP source power. [ABSTRACT FROM AUTHOR]

Abnormalities in skin pigmentation can produce disorders such as albinism or melasma. There is a research need to discover novel compounds that safely and effectively regulate pigmentation. To identify novel modulators of pigmentation, we attempted to purify compounds from a bioactive fraction of the Korean medicinal plant Artemisia capillaris Thunberg. The novel compound isofraxidin 7-O-(6′-O-p-coumaroyl)-β-glucopyranoside (compound 1) was isolated and its pigmentation activity was characterized in mammalian melanocytes. Compound 1 stimulated melanin accumulation and increased tyrosinase activity, which regulates melanin synthesis. Moreover, compound 1 increased the expression of tyrosinase and the key melanogenesis regulator microphthalmia-associated transcription factor (MITF) in melanocytes. Compared to the parent compound, isofraxidin, compound 1 produced greater effects on these pigmentation parameters. To validate compound 1 as a novel hyperpigmentation agent in vivo, we utilized the zebrafish vertebrate model. Zebrafish treated with compound 1 showed higher melanogenesis and increased tyrosinase activity. Compound 1 treated embryos had no developmental defects and displayed normal cardiac function, indicating that this compound enhanced pigmentation without producing toxicity. In summary, our results describe the characterization of novel natural product compound 1 and its bioactivity as a pigmentation enhancer, demonstrating its potential as a therapeutic to treat hypopigmentation disorders. [ABSTRACT FROM AUTHOR]

There is a continual need to develop novel and effective melanogenesis inhibitors for the prevention of hyperpigmentation disorders. The plant Artemisia capillaris Thunberg (Oriental Wormwood) was screened for antipigmentation activity using murine cultured cells (B16-F10 malignant melanocytes). Activity-based fractionation using HPLC and NMR analyses identified the compound 4,5-O-dicaffeoylquinic acid as an active component in this plant. 4,5-O-Dicaffeoylquinic acid significantly reduced melanin synthesis and tyrosinase activity in a dose-dependent manner in the melanocytes. In addition, 4,5-O-dicaffeoylquinic acid treatment reduced the expression of tyrosinase-related protein-1. Significantly, we could validate the antipigmentation activity of this compound in vivo, using a zebrafish model. Moreover, 4,5-O-dicaffeoylquinic acid did not show toxicity in this animal model. Our discovery of 4,5-O-dicaffeoylquinic acid as an inhibitor of pigmentation that is active in vivo shows that this compound can be developed as an active component for formulations to treat pigmentation disorders. [ABSTRACT FROM AUTHOR]

We established and tested an unconstrained sleep apnea monitoring method using a polyvinylidene (PVDF) film-based sensor for continuous and accurate monitoring of apneic events occurred during sleep. Twenty-six sleep apnea patients and six normal subjects participated in this study. Subjects’ respiratory signals were measured using the PVDF-based sensor during polysomnography. The PVDF sensor comprised a 4 × 1 array, and a thin silicon pad was placed over the sensor to prevent damage. Total thickness of the merged system was approximately 1.1 mm which was thin enough to prevent the subject from being consciously aware of its presence. It was designed to be placed under subjects’ backs and installed between a bed cover and mattress. The proposed method was based on the standard deviation of the PVDF signals, and it was applied to a test set for detecting apneic events. The method's performance was assessed by comparing the results with a sleep physician's manual scoring. The correlation coefficient for the apnea-hypopnea index (AHI) values between the methods was 0.94 $(p$ < 0.001). The areas under the receiver operating curves at three AHI threshold levels (>5, >15, and >20) for sleep apnea diagnosis were 0.98, 0.99, and 0.98, respectively. For min-by-min apnea detection, the method classified sleep apnea with an average sensitivity of 72.9%, specificity of 90.6%, accuracy of 85.5%, and kappa statistic of 0.60. The developed system and method can be applied to sleep apnea detection in home or ambulatory monitoring. [ABSTRACT FROM PUBLISHER]

Abstract: Our study investigated the histogenesis and biological significance of spindle cell carcinoma (SpCC) by comparing with moderately-well-differentiated squamous cell carcinoma (SCC) cell lines. Snail mRNA expression was readily detectable in the SpCC cell line, while E-cadherin was undetectable. SpCC cells showed lower proliferative and invasive activities than two other SCC cell lines. Culturing under air–liquid interface conditions promoted squamous cell differentiation, whereas fibroblastic differentiation after submerged culture with collagen, suggesting that the microenvironment may be a regulating factor of spindle cell differentiation as well as Snail expression and spindle cell change may not always entail the invasive behavior. [Copyright &y& Elsevier]

• In-vitro biotransformation of levothyroxine is conducted by S9 fraction. • The biotransformants are predicted by in-silico prediction and validated by LC-MS/MS. • Reporter gene assay is applied to link the activity changes with metabolite profiles. Thyroid-disrupting compounds (TDCs) are chemicals that modify thyroid gland function and disrupt hormonal homeostasis. Like other endocrine-disrupting chemicals (EDCs), TDCs often show altered activities following post-metabolic modification via endogenous enzymatic reaction. Hence, we developed evaluation system consisting of (1) in vitro metabolic reaction module, (2) high-resolution mass-spectrometry, and (3) human cell-based reporter gene assay. We developed the reaction module using rat S9 fraction where levothyroxine (T4) as a model compound, was subjected to phase-I or phase-I+II biotransformation. The metabolic profiles of the biotransformants were systematically configured based on in-silico prediction of potential products and experimental validation using liquid-chromatography Orbitrap mass-spectrometry. Thyroid agonistic activities of the biotransformants were evaluated by thyroid receptor-mediated stably transfected transcriptional activation assay using hTRE_HeLa cells. Indeed, we detected the increased activities following metabolic conversion of T4 in a dose-dependent manner. Note that the activity by phase-I+II reaction was much greater than by phase-I reaction (3.8-fold increase). Subsequently, we explored metabolic signatures, which potentially contributed to the hyperactivity by phase-I+II reaction. A total of 77 metabolic features were annotated based on the in-silico prediction, which included biotransformants with deiodination and conjugation. The glucuronide-conjugated form was found at the highest fold-increase (970-fold increase) whereas marginal increases were determined in the deiodinized forms (1.6-fold increase in T3 and 2.0-fold increase in rT3). Further, the systematic approach was evaluated and comparably analyzed by the metabolic profiles of bithionol, which is structurally related to T4. Our current result suggested the potential application of in vitro evaluation system to risk assessment of thyroid-disrupting activity. [ABSTRACT FROM AUTHOR]

Simple Summary: Few studies have employed expression data of normal tissues to explore the survival of cancer patients. Hence, we identified aging-related genes and microRNAs in normal tissues from patients with various types of cancer and investigated their effects on survival. We built statistical models to predict the survival of cancer patients using the expression levels of aging-related genes and microRNAs. We found that five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) from kidney cancer patients were significantly related to patient survival. We experimentally showed that there is an increase in the five aging-related genes in the macrophages of aged mice and, among these five genes, the invasion of cancer cells is inhibited by downregulating DUSP22. Using the zebrafish model of tumor cell dissemination, it was also confirmed that in vivo treatment with a small molecule inhibitor of DUSP22 blocked the metastasis of cancer cells in the early stage. The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development. [ABSTRACT FROM AUTHOR]

Inflammation-mediated skeletal muscle wasting occurs in patients with sepsis and cancer cachexia. Both conditions severely affect patient morbidity and mortality. Lithium chloride has previously been shown to enhance myogenesis and prevent certain forms of muscular dystrophy. However, to our knowledge, the effect of lithium chloride treatment on sepsis-induced muscle atrophy and cancer cachexia has not yet been investigated. In this study, we aimed to examine the effects of lithium chloride using in vitro and in vivo models of cancer cachexia and sepsis. Lithium chloride prevented wasting in myotubes cultured with cancer cell-conditioned media, maintained the expression of the muscle fiber contractile protein, myosin heavy chain 2, and inhibited the upregulation of the E3 ubiquitin ligase, Atrogin-1. In addition, it inhibited the upregulation of inflammation-associated cytokines in macrophages treated with lipopolysaccharide. In the animal model of sepsis, lithium chloride treatment improved body weight, increased muscle mass, preserved the survival of larger fibers, and decreased the expression of muscle-wasting effector genes. In a model of cancer cachexia, lithium chloride increased muscle mass, enhanced muscle strength, and increased fiber cross-sectional area, with no significant effect on tumor mass. These results indicate that lithium chloride exerts therapeutic effects on inflammation-mediated skeletal muscle wasting, such as sepsis-induced muscle atrophy and cancer cachexia. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is an important posttranscriptional regulatory process. Damaged or unnecessary cells need to be removed though apoptosis to maintain physiological processes. Caspase-2 pre-mRNA produces pro-apoptotic long mRNA and anti-apoptotic short mRNA isoforms through AS. How AS of Caspase-2 is regulated remains unclear. In the present study, we identified a novel regulatory protein SRSF9 for AS of Caspase-2 cassette exon 9. Knock-down (KD) of SRSF9 increased inclusion of cassette exon and on the other hand, overexpression of SRSF9 decreased inclusion of this exon. Deletion mutagenesis demonstrated that exon 9, parts of intron 9, exon 8 and exon 10 were not required for the role of SRSF9 in Caspase-2 AS. However, deletion and substitution mutation analysis revealed that AGGAG sequence located at exon 10 provided functional target for SRSF9. In addition, RNA-pulldown mediated immunoblotting analysis showed that SRSF9 interacted with this sequence. Gene ontology analysis of RNA-seq from SRSF9 KD cells demonstrates that SRSF9 could regulate AS of a subset of apoptosis related genes. Collectively, our results reveal a basis for regulation of Caspase-2 AS. [ABSTRACT FROM AUTHOR]