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Solar activity, such as sunspots and flares, has a great impact on humans, living beings, and technologies in the whole world. Changes in sunspots will influence high-frequency and space-navigation radio communications. Based on the full-disk, southern and northern hemispheres sunspot areas (SAs) data in 1874–2023 from the Royal Observatory, Greenwich (RGO) USAF/NOAA, extreme value theory (EVT) is applied to predict the trend of the 25th and 26th solar cycles (SCs) in this work. Two methods with EVT, the block maxima (BM) approach and the peaks-over-threshold (POT) approach, are employed to research solar extreme events. The former method focuses on each block's maximum sunspot areas value and is applied for the generalized extreme value (GEV) distribution. The latter method aims to select the extreme values exceeding a threshold value and is used to obtain the generalized Pareto (GP) distribution. It is the first time that the EVT is applied on the sunspot areas data from the Royal Observatory, Greenwich (RGO) USAF/NOAA. The analysis indicates that the estimated 8-year return levels for sunspot areas are 5701 and 6258 using the two methods, while the estimated 19-year return levels are all 7165. This suggests that the trends of the 25th and 26th solar cycles will be stronger than that of the 24th solar cycle. [ABSTRACT FROM AUTHOR]

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-35, which has an anti-inflammatory role in acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), is relatively promising as a drug target. Studies have shown that curcumin may play a therapeutic role in ALI and enhance the suppressive function of regulatory T cells (Tregs). To illustrate the effect of curcumin on the regulation of Treg cell differentiation and expression of IL-35, we built a cecal ligation and puncture (CLP)–induced acute lung injury mouse mode with curcumin pretreatment. The expression of IL-35 in serum, severity of lung injury, IL-17A in lung tissue, survival rate, Treg-related cytokines levels in serum, nuclear factor-kappa B (NF-κB)'s nuclear translocation in lung tissue, and splenic CD4+CD25+FOXP3+ Tregs were assessed. Furthermore, the proportion of Tregs, STAT5, and IL-35 expression during naïve CD4+ T cell differentiation in vitro was measured. Compared with the CLP group, the increased IL-35 expression in CLP with the curcumin pretreatment (CLP + Cur) group was consistent with the decreased severity of lung injury, IL-17A protein levels in lung tissue, and Treg-related cytokines levels. Pretreatment with curcumin, the survival rate climbed to 50%, while the mortality rate was 100% in the CLP group. In addition, splenic CD4+CD25+FOXP3+ Treg cells increased in the CLP + Cur group. In vitro, CD4+CD25+FOXP3+ Treg cells from naïve CD4+ T cells, STAT5 proportion, and IL-35 expression increased after curcumin treatment. These findings showed that curcumin might regulate IL-35 by activating the differentiation of Treg cells to control the inflammation in acute lung injury. [ABSTRACT FROM AUTHOR]

Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4+CD25+FOXP3+ Tregs from splenic naïve CD4+ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a spectrum of acute and life-threatening pulmonary inflammatory conditions. Treatment of ALI remains a clinical challenge. Recently, intermittent fasting (IF) has been shown to improve health and alleviate many diseases. In this study, we tested whether IF attenuated ALI and investigated the mechanism underlying this process. In vivo, the effects of IF on ALI were evaluated in a lipopolysaccharide (LPS)-induced murine ALI model. We found that two times of 24-h fasting in a week before ALI efficiently ameliorated LPS-induced lung injury in mice, characterized by alleviated lung lesions, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde content, and lower levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β. In vitro, functional assays were conducted to assess IF on the inflammatory response and macrophage polarization of bone marrow-derived macrophages (BMDMs) treated with LPS or IL-4. And PPARγ antagonist GW9662 and AMPK siRNA were used to test the role of PPARγ and AMPK in the IF-mediated improvement of ALI. The results showed that IF (serum deprivation) suppressed macrophage M1 activation and promoted M2 activation in LPS-treated BMDMs. While, IF also augmented macrophage M2 polarization in IL-4-treated BMDMs. Further mechanistic studies showed that the promotive effect of IF on M2 polarization was related to the activation of the PPARγ and AMPK pathways. In conclusion, this study suggests that IF enhances M2 polarization by activating the AMPK and PPARγ pathways, thus facilitating anti-inflammatory response and ameliorating ALI. [ABSTRACT FROM AUTHOR]

Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy. [ABSTRACT FROM AUTHOR]

Postoperative sore throat (POST) is one of the main postoperative complaints. This study was to evaluate the efficacy of budesonide inhalation suspension (BIS) in reducing the incidence and severity of POST. One hundred and twenty patients scheduled for thyroid surgery with general anesthesia were enrolled and randomized into three groups. Group A received 200 mcg BIS 10 min prior to the tracheal intubation and received the same treatment 6 and 24 h after extubation. Group B received 200 mcg BIS 6 and 24 h after extubation. Control group received the same scheduled treatment as Group A, but the BIS was replaced with 2 ml normal saline. The patients were evaluated for sore throat and hoarseness 1, 24 and 48 h after extubation. The status of laryngopharynx was also recorded. There was no statistically significant difference in the incidence of sore throat among three groups. However, hoarseness occurred significantly less frequently in Group A ( P < 0.05). One hour after extubation, Group A exhibited significantly less severe sore throat and hoarseness compared to the other two groups ( P < 0.05), which disappeared 24 h later. The mucositis scores of laryngopharynx at 1, 24 and 48 h post-extubation were significantly lower in Group A ( P < 0.05). BIS can reduce the incidence and severity of the POST prophylactically. [ABSTRACT FROM AUTHOR]

Purpose: Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury. Methods: In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 μM H2O2 for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches. Results: The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The increased protein levels of HIF-1α, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 μM) and/or significantly (50 and/or 100 μM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively. Conclusion: SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1α, VEGF, and MMP-9. [ABSTRACT FROM AUTHOR]

N-acylethanolamides (NAEs) are a class of naturally occurring lipid molecules with pleiotropic activities ranging from energy homeostasis to analgesic functioning. However, the comprehensive quantitation of endogenous NAEs is challenged by the sub-trace level (nM) in complex biological samples and the limited availability of stable isotope labeled internal standards (SIL-IS). Herein, a sensitive method was developed to accurately determine 20 NAEs in biological samples by chemical isotope labeling strategy coupled with liquid chromatography - tandem mass spectrometry (LC-MS/MS). A pair of efficient derivatization reagents, acetyl chloride- d 0 (ACC- d 0) and acetyl chloride- d 3 (ACC- d 3), were used to label NAEs in biological samples and NAE standard mixture, respectively. The heavily labeled NAE derivatives of the standard substances were used as one-to-one internal standards to minimize the matrix effects and potential ion suppression in MS analysis. Although no chemical moiety with high ionization capability was introduced, the detection sensitivity of the derivatized NAEs were substantially enhanced, as evidenced by 6- to 170-fold increase in LOQs, compared to non-derivatized NAEs. The derivatized NAEs provided the stable and abundant specific product ions in MS/MS spectrum, which were used as the quantitation ions for multiple reaction monitoring (MRM) analysis. The validated LC-MS/MS method was also successfully applied to determine NAEs in serum samples and liver tissues from control and alcohol-fed mice, which shown its practicability in the analysis of endogenous NAE in biological samples. Collectively, the proposed method offers a sensitive and accurate quantification of endogenous NAEs, which may facilitate the understanding of NAE metabolisms and their functions in the physiological and pathological processes. [Display omitted] • A sensitive and accurate LC-MS method was developed to quantify 20 NAEs by chemical isotope labeling. • The detection sensitivity of the derivatized NAEs were substantially enhanced. • The derivatization provided the stable and abundant specific product ions for the quantitation by MRM analysis. • The proposal method was successfully applied to quantify NAEs in serum and liver tissues from alcohol-fed mice. [ABSTRACT FROM AUTHOR]

Based on the daily sunspot number (SN) data (1954–2011) from the Purple Mountain Observatory, the extreme value theory (EVT) is employed for the research of the long-term solar activity. It is the first time that the EVT is applied on the Chinese SN. Two methods are used for the research of the extreme events with EVT. One method is the block maxima (BM) approach, which picks the maximum SN value of each block. Another one is the peaks-over-threshold (POT) approach. After a declustering process, a threshold value (here it is 300) is set to pick the extreme values. The negative shape parameters are obtained by the two methods, respectively, indicating that there is an upper bound for the extreme SN value. Only one value of the N -year return level (RL) is estimated: N = 19 years. For N = 19 years, the RL values of SN obtained by two methods are similar with each other. The RL values are found to be 420 for the POT method and the BM method. Here, the trend of 25th solar cycle is predicted to be stronger, indicating that the length of meridional forms of atmospheric circulation will be increased. [ABSTRACT FROM AUTHOR]

• Inhibition of HMGB1 increased the proportion of Treg and expression of IL-35. • HMGB1 mediates caspase-11-dependent pyroptosis in acute lung injury. • HMGB1 down-regulates Tregs differentiation from CD4+ naïve T cells. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe form of inflammatory lung disease. Its development and progression are regulated by cytokines. The purpose of this study was to determine the effects of HMGB1 involved in the regulation of Treg cells and IL-35. A cecal ligation and puncture (CLP)-induced ALI model was used to investigate the changes in IL-35, Tregs, and the expression of RAGE and caspase-11 after HMGB1 inhibition (glycyrrhizin was used as an inhibitor of HMGB1). CD4+ naïve T cells sorted from C57BL/6 mice spleens were cultured to explore the role of HMGB1 in the differentiation from CD4+ naïve T cells to Tregs. HMGB1 promoted lung injury and uncontrolled inflammation in the CLP mouse model. HMGB1, NF-κB p65, RAGE, and caspase-11 expression in the lungs of CLP mice decreased significantly after pretreatment with glycyrrhizin. We found that the Treg proportion and IL-35 expression were upregulated in the serum and lung of CLP mice after inhibiting HMGB1. In our in vitro experiments, we found that recombinant HMGB1 significantly suppressed the proportion of CD4+CD25+FOXP3+Tregs differentiated from CD4+ naïve T cells. The inhibition of HMGB1 increased the proportion of Treg and expression of IL-35 and alleviated lung injury in the CLP-induced ALI model. Furthermore, inhibition of HMGB1 reduced caspase-11-dependent pyroptosis in the lungs of the CLP-induced ALI model. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is characterized by progressive memory loss and cognitive impairment. The aggregation of amyloid β (Aβ) and hyperphosphorylated tau protein are two major pathological features of AD. Nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, NOX) has been indicated in Aβ pathology; however, whether and how it affects tau pathology are not yet clear. Methods: The role of NOX2 in cognitive function, amyloid plaque formation, and tau hyperphosphorylation were examined in APP/PS1 transgenic mice mated with p47phox-deficient mice (with deletion of the gene of neutrophil cytosolic factor 1, Ncf1) and/or in p47phox-deficient mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ). The cognitive and non-cognitive functions in these mice were assessed by Morris water maze, Rotarod test, open field, and elevated plus maze. Aβ levels, amyloid plaques, p47phox expression, and astrocyte activation were evaluated using immunofluorescence staining, ELISA, and/or Western blotting. Cultured primary neuronal cells were treated with okadaic acid or conditioned media (CM) from high glucose-stimulated primary astrocytes. The alteration in tau pathology was determined using Western blotting and immunofluorescence staining. Results: Deletion of the gene coding for p47phox, the organizer subunit of NOX2, significantly attenuated cognitive impairment and tau pathology in these mice. p47phox deficiency decreased the activation of astrocytes but had no effect on Aβ levels and amyloid plaque formation in the brains of aged APP/PS1 mice, which displayed markedly increased expression of p47phox in neurons and astrocytes. Cell culture studies found that neuronal p47phox deletion attenuated okadaic acid-induced tau hyperphosphorylation at specific sites in primary cultures of neurons. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in primary neurons, whereas this effect was absent from p47phox-deficient astrocytes. Conclusions: These results suggest that p47phox is associated with cognitive function and tau pathology in AD. p47phox expressed in neurons contributes to tau hyperphosphorylation directly, while p47phox in astrocytes affect tau hyperphosphorylation by activating astrocytes indirectly. Our results provide new insights into the role of NOX2 in AD and indicate that targeted inhibition of p47phox may be a new strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1β, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1β, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis. [ABSTRACT FROM AUTHOR]

• Curcumin suppressed inflammatory mediators, alleviated lung injury and increased CD4+CD25+Foxp3+ Tregs in ALI model. • Curcumin can upregulate the differentiation from CD4+ naïve T cells to Tregs in vitro. • Curcumin can promote Tregs ratio and increase Tregs derived IL-10 immune modulation. • Curcumin down-regulates lung M1 macrophages and up-regulates M2 macrophages in ALI. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS. A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested. Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10. Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation. [ABSTRACT FROM AUTHOR]

Background: Single-cell RNA sequencing (scRNA-seq) measurements of gene expression show great promise for studying the cellular heterogeneity of rice roots. How precisely annotating cell identity is a major unresolved problem in plant scRNA-seq analysis due to the inherent high dimensionality and sparsity. Results: To address this challenge, we present NRTPredictor, an ensemble-learning system, to predict rice root cell stage and mine biomarkers through complete model interpretability. The performance of NRTPredictor was evaluated using a test dataset, with 98.01% accuracy and 95.45% recall. With the power of interpretability provided by NRTPredictor, our model recognizes 110 marker genes partially involved in phenylpropanoid biosynthesis. Expression patterns of rice root could be mapped by the above-mentioned candidate genes, showing the superiority of NRTPredictor. Integrated analysis of scRNA and bulk RNA-seq data revealed aberrant expression of Epidermis cell subpopulations in flooding, Pi, and salt stresses. Conclusion: Taken together, our results demonstrate that NRTPredictor is a useful tool for automated prediction of rice root cell stage and provides a valuable resource for deciphering the rice root cellular heterogeneity and the molecular mechanisms of flooding, Pi, and salt stresses. Based on the proposed model, a free webserver has been established, which is available at https://www.cgris.net/nrtp. [ABSTRACT FROM AUTHOR]

Background. Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). Methods. Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. Results. The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P < 0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P < 0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. Conclusion. Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC. [ABSTRACT FROM AUTHOR]

Abstract Background Androgen has been implicated in aging-related cardiac remodeling, but its precise role in aging heart remains controversial. We aimed to investigate the role of testosterone in the development of aging-related cardiac remodeling and the mechanisms involved. Methods Wild type and Axl knockout mice (Axl−/−) were randomized into three groups: the young group (n = 30, 3 months old), the aging group (n = 30, 18 months old), the testosterone undecanoate treatment group (TU, n = 30, 18 months old). Mice in the TU group were given testosterone undecanoate (39 mg/kg) by subcutaneous injection on the back at fifteen-months-old, once a month, a total of three times. The old group received solvent reagent (corn oil) by the same method. Results The aging mice exhibited a decrease in serum testosterone, and Gas6 levels and an increase in apoptosis, and manifested cardiac fibrosis. Testosterone injection to wild type mice increased the levels of testosterone and Gas6 in serum and decreased cardiac apoptosis and fibrosis. Axl−/−mice receiving testosterone injection exhibited no obvious improvement in cardiac remodeling although the levels of testosterone and Gas6 in serum elevated. Conclusions These data indicated that testosterone replacement therapy (TRT) alleviates cardiac fibrosis and apoptosis, at least in part by enhancing Gas6 expression. Moreover, deletion of Axl disables testosterone, which indicated that Axl is an important downstream regulator of testosterone. TRT would improve aging-related cardiac remolding via Gas6/Axl signaling pathway, implicating its therapeutic potential to treat aging-related heart disease. Highlights • Testosterone decreases cardiomyocyte apoptosis in aging mice. • Testosterone ameliorates cardiac fibrosis in aging mice. • Testosterone increases the level of Gas6. • Testosterone protects from cardiac aging in a Gas6/Axl dependent manner. [ABSTRACT FROM AUTHOR]

Background/Aims: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. Methods: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. Results: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-β-Gal, fewer G1 phase cells, and decreased levels of p16INK4a and p21Cip1 expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. Conclusion: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and nicotinamide adenine dinucleotide ( NAD)+ depletion. The cell death and apoptosis of ropivacaine-induced SH- SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD+ level, and western blots were used to analyze the expression levels of PARP-1 and apoptosis-inducing factor ( AIF) after ropivacaine treatments with different concentrations and durations. A PARP-1 inhibitor ( PJ-34) was used to confirm the relationship between PARP-1 activation and NAD+ depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (Δψm) assay were used to detect the role of exogenous NAD+ in ropivacaine-induced neuronal injury. Ropivacaine-induced SH- SY5Y cell death and apoptosis, PARP-1 activation, and AIF increase as well as intracellular NAD+ depletion occurred in a time- and concentration-dependent manner ( P<.05). PARP-1 activation led to NAD+ depletion ( P<.05). Exogenous NAD+ impaired ropivacaine-induced nuclear injury ( P<.05). Ropivacaine treatment induced PARP-1 activation and NAD+ depletion ( P<.05). Parthanatos ( PARP-1-dependent cell death) was definitely involved in ropivacaine-induced neuronal injury, and exogenous NAD+ may be a novel therapeutic method for parthanatos-dependent neuronal injury. [ABSTRACT FROM AUTHOR]

Background: Statins are widely prescribed to reduce cholesterol levels in the prevention of atherosclerotic cardiovascular disease. However, the debate about the effect of statins on cancer risk remains unsettled. The aim of this study was to investigate the association of utilization of statins with the risk of gastric cancer by carrying out a meta-analysis. Methods: A literature search was performed on PubMed and EMBASE up to March 2013 to identify the cohort or case-control studies or randomized controlled trials (RCTs) that examined the relationship between statins use and the risk of gastric cancer. The bibliographies of the retrieved articles were also reviewed to identify additional studies. A random-effects model was used to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs). Results: Three post-hoc analyses of 26 RCTs involving 290 gastric cancers and eight observational studies totaling 7,321 gastric cancers were included. Statins use was shown to be significantly associated with a 27 % reduction in the risk of gastric cancer (RR = 0.73, 95 % CI = 0.58-0.93), with considerable heterogeneity among studies ( I = 88.9 %). Excluding one study in which all subjects are diabetic patients obtained an attenuated, but homogeneous result (RR = 0.85, 95 % CI = 0.80-0.91, I = 0.0 %). These findings were consistent in the subgroup analysis. Conclusion: A meta-analysis of existing evidence, primarily from observational studies, indicates that use of statins reduces the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

GeSe 2 Nano-Films (GeSe 2 NFMs) were prepared by chemical vapor deposition (CVD). The nanostructures of the GeSe 2 NFMs were revealed by X-ray diffraction and Raman spectroscopy, respectively. The linear optical properties of the samples have been studied by absorption spectroscopy. The nonlinear optical properties of the GeSe 2 NFMs have been studied by Z-scan technique with femtosecond pulses at the wavelength of 1030 nm. The measured band gap of GeSe 2 NFMs is 2.33eV, and the nonlinear absorption coefficient β eff is about 1.344*10−7 cm/W, which is a saturated absorption. In addition, in the fluorescence emission spectrum of GeSe 2 NFM, we found emission peaks in the red and infrared light regions with a wavelength of 760 nm. We found that GeSe 2 NFMs prepared by CVD has a larger band gap and a larger nonlinear absorption coefficient than the doped GeSe 2. These studies indicate the application of GeSe 2 NFMs in laser emitters and nonlinear optical devices, and also provide a reference for subsequent research on nonlinear optical characteristics. • Graphene-structure GeSe 2 nano-films (NFMs) were prepared by Chemical Vapor Deposition. • The GeSe 2 NFM prepared by chemical vapor deposition has good uniformity and compactness. • The nonlinear optical properties of GeSe 2 NFMs prepared by CVD are superior to those prepared by other methods. [ABSTRACT FROM AUTHOR]