Search

To explore the main active components and effects of cell cycle regulation mechanism of Astragali radix (AR) and Angelicae sinensis radix (ASR) on oxidative damage in vascular endothelial cells, a model of oxidative damage in human umbilical vein endothelial cells (HUVECs) induced by oxidized low-density lipoprotein (ox-LDL) treatment was developed. Based on the "knock-out/knock-in" model of the target component, cell viability, intracellular reactive oxygen species (ROS), and lactate dehydrogenase (LDH) leakage were assessed by Cell Counting Kit-8 assay, fluorescent probe 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA), and colorimetric assay, respectively, to evaluate the protective effect of the active components of AR and ASR (astragaloside IV (AS IV), astragaloside I (AS I), formononetin (FRM), calycosin (CAL), calycosin-7-O-β-D glucoside (CLG), and ferulic acid (FRA)) against oxidative damage. The cell cycle and expression of genes encoding cyclins and cyclin-dependent kinases (CDKs) were observed using flow cytometry and quantitative real-time polymerase chain reaction. The results showed that the combination of active components (ACC) significantly inhibited the decrease in cell viability as well as the increase in ROS and LDH release in HUVECs induced by ox-LDL treatment. AS IV and FRM promoted the proliferation of HUVECs but the proliferation index was decreased in the AS I and FRA groups; this inhibitory effect was counteracted by the ACC. The ACC reduced and increased the proportion of positive cells in G1 and S phases, respectively, followed by the upregulation of cyclin A (CCNA), cyclin E (CCNE), and CDK2 mRNA expression and downregulation of cyclin B (CCNB), cyclin D1 (CCND1), CDK1, CDK4, and CDK6 mRNA expression, which significantly mitigated inhibition of HUVECs proliferation induced by ox-LDL treatment. Taken together, AS IV, AS I, FRM, CAL, CLG, and FRA were the primary pharmacodynamic substances of AR and ASR that alleviated oxidative injury in HUVECs. ACC mitigated the upregulation of intracellular ROS levels and LDH release induced by ox-LDL treatment, which promoted the cell cycle procession of HUVECs by regulating the expression of genes encoding cyclins and CDKs and thus preventing oxidative damage in HUVECs. [ABSTRACT FROM AUTHOR]

Objective: To analyze the correlation between the Kellgren–Lawrence (K‐L) score of knee osteoarthritis (KOA) patients with different degrees and their urine concentration of C‐terminal telopeptide of collagen type II (CTX‐II) and interleukin‐1β (IL‐1β), and to further evaluate the diagnostic value of CTX‐II and IL‐1β during the pathological process by producing an experimental osteoarthritis (OA) model in rabbits. Methods: From 1 January 2017 to 31 December 2018, a total of 34 subjects (7 mild, 9 moderate, 9 severe arthritis patients, and 9 healthy individuals) comprising 16 men and 18 women were included in this study. Patients were diagnosed according to the American College of Rheumatology (ACR) criteria. The urine of all subjects was collected to detect the concentration of CTX‐II and IL‐1β. The rabbits in the KOA group were subjected to protease (control group with saline) injection into the articular cavity of their right knees and immobilization with gypsum. We used radiological and histological examination to identify the KOA model. ELISA was applied to investigate the concentrations of CTX‐II and IL‐1β in urine and serum, and Spearman's rank correlation analysis was used to analyze the correlation. Results: There was no significant difference in the mean ages and body mass index (BMI) between groups. The mean ages of mild, moderate, and severe arthritis patients and healthy individuals were 54.29 ± 5.76, 58.44 ± 6.44, 59.89 ± 6.75, and 56.67 ± 4.18 years, respectively. The mean BMI of mild, moderate, and severe arthritis patients and healthy individuals were 23.59 ± 1.56, 23.57 ± 2.06, 24.46 ± 1.64, and 23.42 ± 1.35 kg/m2, respectively. The Kellgren–Lawrence (K‐L) score was higher with the aggravation of KOA. The K‐L scores of mild, moderate, and severe KOA patients were 1.14 ± 0.38, 2.56 ± 0.53, and 3.63 ± 0.52, respectively. The KOA symptoms of patients became more severe, with not only increased K‐L scores but also elevated concentrations of CTX‐II and IL‐1β. Moreover, there was a positive correlation between CTX‐II and IL‐1β of all subjects (r = 0.974, P < 0.001), between K‐L score and urine concentration of CTX‐II (r = 0.900, P < 0.001), and between K‐L score and IL‐1β (r = 0.813, P < 0.001) of all subjects. Both were significantly increased in KOA group rabbits at all time points after surgery. The serum concentration of CTX‐II and IL‐1β was elevated as early as in the 2nd week (3.69 and 4.25 times) and reached a peak (5.41 and 7.23 times) in the 4th week after surgery. Then, until 12 weeks after surgery, the CTX‐II and IL‐1β concentrations in the KOA group were slightly reduced and remained around 4.5 and 6.3 times that in the control group. Moreover, there was a positive correlation between the serum concentration of IL‐1β and CTX‐II (r = 0.967, P < 0.001). Conclusion: CTX‐II and IL‐1β, which were significantly increased during the process of KOA, can be used as biomolecular markers to provide guidelines for early diagnosis and treatment of KOA. [ABSTRACT FROM AUTHOR]

Oxidative stress induced by hypoxia/ischemia resulted in the excessive reactive oxygen species (ROS) and the relative inadequate antioxidants. As the initial barrier to environmental pollutants and allergic stimuli, airway epithelial cell is vulnerable to oxidative stress. In recent years, the antioxidant effect of hydrogen sulfide (H2S) has attracted much attention. Therefore, in this study, we explored the impact of H2S on CoCl2-induced cell injury in 16HBE14o- cells. The effect of CoCl2 on the cell viability was detected by Cell Counting Kit (CCK-8) and the level of ROS in 16HBE14o- cells in response to varying doses (100–1000 μmol/L) of CoCl2 (a common chemical mimic of hypoxia) was measured by using fluorescent probe DCFH-DA. It was shown that, in 16HBE14o- cells, CoCl2 acutely increased the ROS content in a dose-dependent manner, and the increased ROS was inhibited by the NaHS (as a donor of H2S). Moreover, the calcium ion fluorescence probe Fura-2/AM and fluorescence dye Rh123 were used to investigate the intracellular calcium concentration ([Ca2+]i) and mitochondria membrane potential (MMP) in 16HBE14o- cells, respectively. In addition, we examined apoptosis of 16HBE14o- cells with Hoechst 33342. The results showed that the CoCl2 effectively elevated the Ca2+ influx, declined the MMP, and aggravated apoptosis, which were abrogated by NaHS. These results demonstrate that H2S could attenuate CoCl2-induced hypoxia injury via reducing ROS to perform an agonistic role for the Ca2+ influx and MMP dissipation. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation. The corresponding author failed to provide a satisfactory explanation. The editors therefore feel that the findings of the manuscript cannot be relied upon and that the article needs to be retracted. [ABSTRACT FROM AUTHOR]

Detecting the state mechanism of protocol can effectively improve the test comprehensiveness when testing the stability of network. This paper proposed a detection method of the state mechanism of protocol based on finite state machine. First, this method established an FSM model of certain message sending entity of testing protocol and determined the input set. Second, during the test, it monitored state transitions of sending entity and generated a state transition diagram. Finally, it determined the state mechanism of protocol message and defined trigger conditions of stateful message according to the state transition diagram. It determined the state mechanism of protocol after summarizing and classifying the tested messages. This paper built a lab environment to test and verify the effectiveness of this method. [ABSTRACT FROM AUTHOR]

A flexible dicarboxylic acid, 4,4'-{[1,3-phenylenebis-(methylene)]bis(oxy) dibenzoic acid (H 2 L), in combination with 1,10-phenanthroline (phen) was used to reacted with Zn(II) ions under hydrothermal conditions, successfully affording a new metal-organic framework of [Zn(L)(phen)(H 2 O)] n (1). Luminescence sensing property investigations indicate that, compound 1 is sensitive detector of Fe3+ ions based on quenching of luminescence. Its treatment activity on the child allergic purpura was assessed and the specific mechanism of the compound was explored at the same time. First of all, the content of the inflammatory cytokine released into the skin tissue was measured with ELISA detection kit after the compound treatment. Apart from this, the activation ability of the AMPK inflammatory signaling pathway was measured with real time RT-PCR. [Display omitted] • A new Zn(II)-based compound has been prepared. • It can be used as a sensor for Fe3+ ​ion. • It has the potential choice for the allergic purpura therapy. [ABSTRACT FROM AUTHOR]

Disseminated intravascular coagulation (DIC) and abdominal compartment syndrome (ACS) are rare complications of pregnancy, and even more rare are cases with both complications occurring concomitantly. Obstetricians are relatively unfamiliar with these types of cases, the majority of which are fatal. We describe here a primigravida with acute fatty liver of pregnancy and a multipara with placental abruption who each developed uterine inertia complicated by postpartum DIC that required total hysterectomy. They developed ACS postoperatively and required decompressive laparotomy to alleviate increased intra-abdominal pressure and end-organ dysfunction. After timely decompressive laparotomy, both patients recovered without any additional complications and were discharged within 4 weeks of their initial admission. These 2 cases serve to remind obstetricians to consider the possibility of ACS whenever there is a fresh wound in the abdominal cavity of a patient with postpartum DIC. However, even when there is severe deterioration in the condition of a patient with ACS, immediate decompressive laparotomy may not be appropriate; the timing of the procedure is very important. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: To investigate the renal microvascular injury in acute aristolochic acid nephropathy (AAN) and the protective effects of prostaglandin E1 (PGE1) in acute AAN. Methods: Female Sprague--Dawley rats were randomly divided into three groups. The rats in PGE1 group received Caulis Aristolochia manshuriensis (CAM) decoction by gavage for 5 days, and PGE1 was given by vena caudalis before gavage. The rats in model group were gavaged with CAM for 5 days, and the same dose of 0.9%% physiologic saline was given by vena caudalis. The rats in control group only received an equal daily volume of saline solution by gavage. Animals were killed at days 3, 5, and 7. Blood urea nitrogen (BUN), serum creatinine, and urinary protein were monitored before killing. Microvascular density was determined by JG12 immunostaining. The expression of angiogenic factor was assessed by vascular endothelial growth factor (VEGF). Tubulointerstitial hypoxia was assessed by hypoxia-inducible factor-1αα (HIF-1αα) expression. Results: CAM induced a significant decrease in VEGF expression and microvascular density in the kidney tissue, accompanied by a significant increase in HIF-1αα, which reduced renal function and increased 24-h urinary protein excretion rates. PGE1 lessened the capillary loss, relieved hypoxia, and protected renal function. No significant pathological changes were found in control rats. Conclusion: The renal microvascular injury in acute AAN is severe. PGE1 can significantly ameliorate the renal microvascular injury, relieve hypoxia, and protect renal function. [ABSTRACT FROM AUTHOR]

Abstract: A new grating structure of cladding being etched as hyperbolic function along the grating length is introduced to improve their performance. The fiber grating exhibits a flattop spectrum with steep edges and high reflectivity when tension is applied to it. The bandwidth utilization defined as the ratio of −1:−30 could be achieved a larger value (>0.9689). The −3dB bandwidth and the bandwidth utilization could be tunable with the increment of tension applied to the grating and the etch factor. [Copyright &y& Elsevier]

Aims: Low caspofungin exposure is frequently encountered in patients with invasive candidiasis caused by Candida albicans. This study aimed to investigate the effects of caspofungin on C. albicans at sub‐inhibitory concentrations. Methods and Results: First, a comparative transcriptomics analysis was performed on C. albicans receiving caspofungin at sub‐minimum inhibitory concentrations (sub‐MICs). The results showed that caspofungin significantly changed the mRNA expression profile in DAY185, with DE‐mRNAs enriched in the functions of cell wall biosynthesis, metabolism, etc. Subsequently, cellular fitness, cell aggregation, energy metabolism activity and the proportion of persister cells of C. albicans were quantitatively and/or qualitatively assessed after sub‐MIC caspofungin exposure. No significant changes in cell fitness and aggregation formation were observed during treatment of C. albicans with sub‐MIC caspofungin. In C. albicans aggregation treated with sub‐MIC caspofungin, we observed a decrease in respiratory metabolism and an increase in persister cells; this effect was more pronounced in als1ΔΔ than in DAY185. Conclusions: Pre‐exposure to sub‐MIC caspofungin suppresses C. albicans respiratory metabolism and promotes persister cell development. Significance and Impact of the Study: Caspofungin should be used with caution in patients with C. albicans infections, as anti‐infection therapy may fail due to persister cells. [ABSTRACT FROM AUTHOR]

Sustainable and eco-friendly sewage sludge treatment and disposal are crucial for pollution prevention, resource utilization, and control. This study used solid sewage sludge and Pistia stratiotes to produce high-performance biochar through modification and high-temperature pyrolysis. The resulting biochar was used to adsorb ammonia nitrogen and phosphate in wastewater, leading to the development of a green and safe value-added fertilizer. Results showed that the combination of Pistia stratiotes and chemical modification optimized the biochar's pore structure, enhanced chemical functional groups, and immobilized heavy metals. The pseudo-second-order kinetic model and Langmuir isotherm model provided better fitting for the adsorption process. The combination of magnesium chloride and Pistia stratiotes treatment exhibited the highest adsorption performance for ammonia nitrogen and phosphate, with maximum theoretical saturation capacities of 62.47 mg g−1 and 33.56 mg g−1. BET, FTIR, and SEM-EDS analysis revealed that surface functional groups, ion exchange, chemical co-precipitation, electrostatic adsorption, and physical adsorption were the main adsorption mechanisms. Regarding desorption, the ammonia nitrogen and phosphate release rates of the value-added fertilizer were remarkably low during the rapid release stage (0–40 min), with only 20.34% and 33.97%, respectively. Moreover, in a pot experiment, the showed greater potential for lettuce growth compared to raw biochar, especially when modified with magnesium chloride, resulting in a 53.78% increase in lettuce biomass. In conclusion, the proposed approach for sewage sludge treatment and disposal offers significant environmental and agricultural benefits through solid waste resource utilization ammonia nitrogen-phosphate recovery from wastewater. [Display omitted] • High-Performed biochar was prepared from Sewage Sludge and Pistia stratiotes • Sludge-biochar emhanced nitrogen-phosphorus recovery from wastewater. • Modified biochar exhibits a slow-release effect for nitrogen and phosphorus. • Sludge-biochar value-added fertilizer has greater potential for lettuce growth. • Proposed approach provides sustainable waste management and nutrient recovery model. [ABSTRACT FROM AUTHOR]

Hospital-acquired pneumonia caused by Acinetobacter baumannii is a major healthcare burden. Type VI Secretion System (T6SS) contributes to both virulence and drug resistance in this bacteria. This study aims to investigate the diagnostic value of hemolysin co-regulated protein (Hcp) gene in A. baumannii pneumonia and further explore the effect of hcp on clinical, pathogenicity and drug resistance. 53 clinical A. baumannii strains from patients' respiratory tract at a teaching hospital were included in this study. Real-time quantitative polymerase chain reaction (qRT-PCR) was carried out to examine the expression of hcp. Recombinant Hcp expression plasmids (pET-28a(+)-hcp) were constructed and his-tagged Hcp were purified to stimulate Tohoku Hospital Pediatrics-1 (THP-1) macrophages. Nuclear Factor Kappa B p65 (NF-κBp65) and Interleukin 8 (IL-8) were detected by qRT-PCR. Antimicrobial susceptibility testing (AST) were examined by an automated instrument system. Hcp gene had 92.6% sensitivity and 75% specificity for distinguishing invasive or colonizing A. baumannii from the respiratory tract. His-tagged Hcp induced NF-κBp65 and IL-8 at gene level in THP-1 macrophages. Additional, high hcp expression isolates showed higher rate of antimicrobial agent exposure (< 30 days) of carbapenems, antibiotic combination therapy and multiple or extensive drug-resistant (MDR/XDR) and exhibited higher resistance rate to clinical commonly-used antimicrobial agents. Hcp gene could serve as a novel diagnostic biomarker to distinguish A. baumannii respiratory tract infection from colonization and participate in eliciting inflammatory responses in vitro. T6SS/hcp may play a role in the development of carbapenem-resistant A. baumannii (CRAB), multiple or extensive drug-resistant A. baumannii (MDRAB/XDRAB). [ABSTRACT FROM AUTHOR]

Objective: To study the effect of borneol combined with astragaloside IV and Panax notoginseng saponins (BAP) on promoting neurogenesis by regulating microglia polarization after cerebral ischaemia–reperfusion(CI/R) in rats. Methods: A focal CI/R injury model was established. Evaluated the effects of BAP on ischaemic brain injury, on promoting neurogenesis, on inhibiting Inflammatory microenvironment and TLR4/MyD88/NFκB signalling pathway. A microglia oxygen-glucose deprivation reoxygenation (OGD/R) model was established that evaluated the effects of BAP on regulating the polarization of microglia and inflammatory microenvironment. Results: BAP can inhibit the expression of TLR4, MyD88 and NFκB proteins, reduce IL-1β and increase IL-10, reduce M1 type microglia and increase M2 microglia. The proliferation of neural stem cells increased, synaptic gap decreased, synaptic interface curvature increased, expression of SYN and PSD95 proteins increased, which improved the neurological dysfunction and reduced the volume of cerebellar infarction and nerve cell injury. Conclusion: BAP can reduce CI/R injury and promote neurogenesis, the effect is related to inhibition of the activation of TLR4/MyD88/NFκB, regulating the polarization of microglia from M1 type to M2 type and inhibition of inflammatory response. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the treatment of pregnancies in different stages complicated by TRAP sequence at a single medical center in China.Study Design: A retrospective study evaluating 25 pregnancies with TRAP sequence was performed at Shengjing Hospital in Shenyang, Liaoning between 2012 and 2016. Patients were diagnosed by ultrasound and categorized into three groups (Ia, IIa and IIb) and were expectantly managed or performed RFA (radiofrequency ablation) according to their stage of TRAP sequence. Perinatal outcomes and survival rates were analyzed.Results: There were four cases in stage Ia, 19 cases in stage IIa, and two cases in stage IIb. Cases in stage Ia were expectantly managed. Among cases in stage IIa, we performed RFA (radiofrequency ablation) in 10 cases and expectant management in 6 cases, with the remainder of the patients refusing intrauterine treatment. We applied RFA to treat one case in stage IIb and the other was managed expectantly. For expectant management group and the RFA group, the survival rates were both 64%(7/11). All pump twins in stage Ia survived and the average gestational age at delivery was 37.9 weeks. In stage IIa, the overall survival rate of the pump twin was 70% (7/10) and the average gestational age at delivery was 35.8 weeks in cases treated by RFA. The survival rate was 50% (3/6) and the average gestational age at delivery was 32.8 weeks in expectantly managed cases in stage IIa. No pump twin survived in stage IIa without treatment (3 cases refused any therapy who were excluded) or in stage IIb.Conclusion: Expectant management is effective for treatment of TRAP sequence in stage Ia. In stage IIa, RFA improves the prognosis of pump twins. [ABSTRACT FROM AUTHOR]

Previous studies investigating the relationship between passive maternal smoking and preterm birth reveal inconsistent results. We conducted the current meta-analysis of observational studies to evaluate the relationship between passive maternal smoking and preterm birth. We identified relevant studies by searching PubMed, EMBASE, and ISI Web of Science databases. We used random-effects models to estimate summary odds ratios (SORs) and 95% confidence intervals (CIs) for aforementioned association. For the analysis, we included 24 studies that involved a total of 5607 women who experienced preterm birth. Overall, the SORs of preterm birth for women who were ever exposed to passive smoking versus women who had never been exposed to passive smoking at any place and at home were 1.20 (95%CI = 1.07–1.34,I2 = 36.1%) and 1.16 (95%CI = 1.04–1.30,I2 = 4.4%), respectively. When we conducted a stratified analysis according to study design, the risk estimate was slightly weaker in cohort studies (SOR = 1.10, 95%CI = 1.00–1.21,n = 16) than in cross-sectional studies (SOR = 1.47, 95%CI = 1.23–1.74,n = 5). Additionally, the associations between passive maternal smoking and preterm birth were statistically significant for studies conducted in Asia (SOR = 1.26, 95%CI = 1.05–1.52), for studies including more than 100 cases of preterm birth (SOR = 1.22, 95%CI = 1.05–1.41), and for studies adjusted for maternal age (SOR = 1.27,95%CI = 1.09–1.47), socioeconomic status and/or education (SOR = 1.28, 95%CI = 1.10–1.49), body mass index (SOR = 1.33, 95%CI = 1.04–1.71), and parity (SOR = 1.27, 95%CI = 1.13–1.43). Our findings demonstrate that passive maternal smoking is associated with an increased risk of preterm birth. Future prospective cohort studies are warranted to provide more detailed results stratified by passive maternal smoking during different trimesters of pregnancy and by different types and causes of preterm birth. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the effect of waterborne copper (Cu) exposure on carnitine concentration, carnitine palmitoyltransferases I (CPT I) kinetics, and expression levels of four CPT I isoforms in the liver, muscle and heart of yellow catfish Pelteobagrus fulvidraco . Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure increased maximal reaction rates (Vmax) in the liver and muscle, but not in the heart. Michaelis–Menten constants (Km) tended to increase in the liver, but decreased in the heart after Cu exposure. The contents of total carnitine (TC) and acylcarnitine (AC) in the liver, and free carnitine (FC) in the muscle increased with increasing waterborne Cu concentrations, while FC content in the muscle declined with the increase of Cu levels. Waterborne Cu exposure also significantly influenced carnitine composition and profiles in heart. The mRNA expression of CPT Iα1a, CPT Iα1b and CPT Iα2a in the liver, and CPT Iα1a, CPT Iα1b and CPT Iβ in the muscle as well as CPT Iα1a in the heart were up-regulated by Cu exposure. Additionally, correlations were observed in the expression levels of CPT I isoforms and Km for carnitine, and between CPT I isoform expression and CPT I activity. To our knowledge, for the first time, the present study provided evidence that waterborne Cu exposure could influence carnitine composition, CPT I kinetics and mRNA levels of four CPT I isoforms in yellow catfish, which served to increase our understanding of the mechanisms underlying lipid catabolism during Cu exposure. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the effect of dietary Cu deficiency and excess on carnitine status, kinetics and expression of CPT I in the liver and muscle of juvenile yellow catfish Pelteobagrus fulvidraco . To this end, yellow catfish were fed 0.76 (Cu deficiency), 4.18 (adequate Cu) and 92.45 (Cu excess) mg Cu kg − 1 diet, respectively, for 8 weeks. In the liver, Cu deficiency did not significantly affect the contents of FC, TC and AC, and the ratios of AC/FC and FC/TC. However, Cu excess reduced FC, TC and AC contents, and the ratio of AC/FC, but increased FC/TC ratio. In the muscle, dietary Cu levels showed no significant effects on the contents of FC, TC and AC as well as the ratio of FC/TC, but Cu excess significantly increased the ratio of AC/FC. Compared to the adequate Cu group, dietary Cu deficiency did not significantly affect the Vmax and Km values, and the ratio of Vmax/Km in the liver and muscle. However, Cu excess decreased Vmax and Vmax/Km ratio in the liver, and increased Vmax in the muscle. The mRNA expression of CPT Iα1a, CPT Iα1b, CPT Iα2a and CPT Iβ in the liver and muscle was influenced by dietary Cu levels. To our knowledge, the present study provided, for the first time, evidence that dietary Cu deficiency and excess differentially influenced carnitine status, kinetics and expression profiles of CPT I of yellow catfish, which would extend our understanding on Cu nutrition in fish. [ABSTRACT FROM AUTHOR]

Embryonic stem cells (ESCs) are a population of pluripotent cells which can differentiate into different cell types. However, there are few reports with regard to differentiate ESCs into epidermal cells in vitro. In this study, we aimed to investigate differentially methylated promoters involved in process of differentiation from ESCs into epidermal-like cells (ELCs) induced by human amnion. We successfully induced ESCs into ELCs, which expressed the surface markers of CK19, CK15 and β1-integrin. With MeDIP-chip arrays, we identified 3435 gene promoters to be differentially methylated, involving 894 HCP (high CpG-containing promoter), 974 ICP (intermediate CpG-containing promoter) and 1567 LCP (low CpG-containing promoter) among all the 17 500 DNA methylation regions of gene promoters in both ESCs and ELCs. Gene oncology and pathway analysis demonstrated that these genes were involved in all the three categories of GO enrichment analysis, including biological process, molecular function and cellular component. All these data suggested that embryonic stem cells can differentiate into epidermal-like cells and promoter methylation is of great importance in this process. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

For the purpose of a quantitative understand for IMS network's attack effect, this paper introduced an evaluation method for IMS's attack effect based on fuzzy comprehensive evaluation. It constructed the attack index tree on the basis of analyzing the possible attack flow, and introduced analytic hierarchy process to compute the indexes' power, and made comprehensive evaluation for IMS attack effects using the fuzzy comprehensive evaluation. To reduce the warp brought by the single fuzzy operator's properties, it selected several operators with different properties to evaluate and took the mean as the finally result. Finally, the examples validate the evaluation method is able to distinguish the attack effects resulted by different attack methods effectively, and can provide a reference to the security of IMS. [ABSTRACT FROM AUTHOR]

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)‐induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell‐specific ITGB4 knockout (ITGB4−/−) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4−/− mice showed increased macrophages (mainly M1‐type macrophages) and neutrophil infiltration into the lungs; inflammation‐related proteins including interleukin (IL)‐6, tumor necrosis factor, and IL‐17A were significantly elevated compared to their levels in ITGB4+/+ mice. Furthermore, we investigated the role of ITGB4 in the anti‐inflammatory response. Intriguingly, in the ITGB4−/− + LPS group, we found significantly reduced expression of anti‐inflammatory factors, including IL‐10 messenger RNA (mRNA) and ARG‐1 mRNA. We also observed that monocyte chemotactic protein (MCP‐1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP‐1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS‐induced ALI. [ABSTRACT FROM AUTHOR]

Highlights: [•] Waterborne Zn exposure differentially affects carntine composition in fish. [•] Differential effect on CPT I kinetics is found in fish exposed to Zn. [•] Zn differentially affects the mRNA levels of four CPT I isoforms in fish. [•] Zn changes CPT I kinetics via altering its expression and carnitine status. [Copyright &y& Elsevier]

Abstract: The present study is conducted to determine the potential mechanisms of Zn on hepatic lipid deposition and metabolism for yellow catfish Pelteobagrus fulvidraco with 8-week chronic exposure to low Zn levels (Zn levels: 0.05, 0.35 and 0.86mg/l Zn, respectively) and 96-h acute exposure to a high Zn level (Zn level: 4.71mg/l Zn, respectively). For that purpose, hepatic lipid deposition and Zn accumulation, hepatic carnitine palmitoyltransferase I (CPT I) and lipoprotein lipase (LPL) activities, and the hepatic mRNA expression of ten genes involved in lipid metabolism are determined. Chronic (8 weeks) exposure to low Zn levels apparently increases hepatic lipid content, hepatosomatic index (HSI) (P <0.05) and LPL activity, and reduces hepatic CPT I activity. In contrast, the acute (96h) exposure to high Zn level reduces hepatic lipid content, HSI and LPL activity, and increases CPT I activity. The change of mRNA levels of genes related to lipid metabolism is Zn concentration-dependent. Pearson correlations among mRNA expression levels, lipid content, CPT I and LPL activities in liver are also observed in yellow catfish with the 8-week chronic Zn exposure. For the first time, our study demonstrates the effect of waterborne Zn exposure on lipid metabolism at the molecular levels in fish, which may contribute to understanding the mechanism of Zn-induced hepatic toxicity in fish. [Copyright &y& Elsevier]

An 8-week feeding trial was conducted to determine the effect of dietary conjugated linoleic acid ( CLA) on growth performance, muscle fatty acid profile, hepatic intermediary metabolism and antioxidant responses in genetically improved farmed Tilapia ( GIFT) strain of O reochromis niloticus (initial body weight: 42.6 ± 0.4 g, mean ± standard deviation). Three replicated groups of GIFT strain of Nile tilapia were hand-fed to satiation, twice a day, with the diets in which CLA oil, containing mainly the bioactive cis-9, trans-11 and trans-10, cis-12 isomers, was included at 0 (control), 0.5%, 1%, 1.5%, 2% and 2.5%, respectively, at the expense of fish oil to maintain the constant lipid and energy levels. Growth performance and feed utilization showed no significant differences among the treatments ( P > 0.05). The dietary inclusion of CLA modified total percentages of the main groups of fatty acids. Increasing saturated fatty acid content and reduced mono-unsaturated fatty acid contents in muscle were observed with increasing dietary CLA inclusion ( P < 0.05). Total n-3 fatty acids and total polyunsaturated fatty acids tended to decline with increasing dietary CLA levels ( P < 0.05), but n-6 fatty acids showed no significant differences among the treatments ( P > 0.05). Dietary CLA supplementation resulted in the significant increase in the trans-10, cis-12 and cis-9, trans-11 CLA isomers in muscle ( P < 0.05) and also significantly influenced several hepatic enzymatic activities, such as succinate dehydrogenase, lactate dehydrogenase, malic dehydrogenase, lipoprotein lipase and hepatic lipase activities ( P < 0.05). Reduced superoxide dismutase and glutathione peroxidase activities, and the decline in malondialdehyde levels were observed in fish fed the CLA-supplemented diets ( P < 0.05), indicating that dietary CLA supplementation showed a powerful antioxidant effect for this fish species. Our study was the first report involved in the effect of dietary CLA inclusion on hepatic intermediary metabolism and antioxidant responses in fish, which could be used as indicators of nutritional and physiological status of the fish species. [ABSTRACT FROM AUTHOR]

Agriculture is a primary contributor of greenhouse gas emissions and thus plays an important role in global climate change. Assessments of the carbon footprints of agricultural products are therefore helpful in climate change mitigation. The objective of this study was to provide a quantitative estimate of the carbon footprint of spring maize ( Zea mays L.) production under different cultivation patterns. Four cultivation patterns were assessed in this study: traditional pattern, optimal pattern, super-high-yield pattern, and high-yield and high-efficiency pattern. The results showed that the greenhouse gas emissions from the agricultural inputs were 3225.2, 3152.9, 4557.2, and 4259.7 kg CO 2 -eq ha −1 for the traditional, optimal, super-high-yield, and high-yield and high-efficiency patterns, respectively, in the spring maize production process. Fertilizers, including chemical fertilizers and organic fertilizer, predominated among the contributors of total greenhouse gas emissions from agricultural inputs, accounting for 66.8, 65.9, 76.1, and 74.4% among the traditional, optimal, super-high-yield, and high-yield and high-efficiency patterns, respectively. The carbon footprint per yield among different cultivation patterns ranged from 0.48 kg CO 2 -eq kg −1 in the traditional pattern to 0.64 kg CO 2 -eq kg −1 in the high-yield and high-efficiency pattern, with intermediate values for the super-high-yield and optimal patterns. The N 2 O from soil and fertilizer application was the greatest contributor to the carbon footprint in spring maize production. Overall, higher yield and lower carbon footprint were concurrently observed under the super-high-yield pattern in the current study. Moreover, a reduction in the rate of fertilizers may provide a potential solution for reducing the carbon footprint of spring maize. [ABSTRACT FROM AUTHOR]

Background: To analyze existing cohort studies and provide evidence for the use of prenatal selective serotonin reuptake inhibitor (SSRI) monotherapy and the associated risk of gestational hypertension and preeclampsia. Methods: A comprehensive search of English language articles published before 30th April 2017 was conducted on PubMed, EMBASE, and the Web of Science databases. Using data acquired, we summarized the relative risks (RRs) and 95% confidence intervals (CIs) of gestational hypertension and preeclampsia using the random-effects model. Heterogeneity between studies was also assessed with the I2 statistic. Results: Seven cohort studies with 1,108,261 individuals were included for analysis. Compared with nonusers, those undertaking prenatal SSRI monotherapy were more likely to develop gestational hypertension or preeclampsia (summarized RR = 1.21, 95% CI: 1.05–1.40, I2 = 71.3%), gestational hypertension (summarized RR = 1.14, 95% CI: 1.00–1.30, I2 = 5.7%), and preeclampsia (summarized RR = 1.32, 95% CI: 0.99–1.78, I2 = 83.3%). In addition, although subgroup analyses, which were stratified by study design, number of cases, geographic location, duration of SSRI monotherapy, registry databases, and adjustment for potential confounders and risk factors, were consistent with the main findings, not all of these showed statistical significance. No evidence of publication bias was detected. Conclusions: Women who receive SSRI monotherapy during pregnancy are at increased risk of gestational hypertension and preeclampsia. [ABSTRACT FROM AUTHOR]

Aims To investigate the safety of fluoxetine use during pregnancy, and to better understand the relationship between maternal fluoxetine use during the first trimester and congenital malformations in infants. Methods PubMed and Web of Science databases were systematically searched from inception to 21 March 2016. Additional studies were identified in a manual search of the reference lists. Two reviewers independently extracted data. A third reviewer checked the data. Estimates were pooled using a random-effects model to calculate the summarized relative ratios (RR) and 95% confidence intervals (CI). Results Among 1918 initially identified articles, 16 cohort studies were included. The offspring of pregnant women exposed to fluoxetine during the first trimester had a statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08-1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95% CI = 1.12-1.73) with low heterogeneity in infants. There were no significant observations of other system-specific malformations in the nervous system, eye, urogenital system, digestive system, respiratory system, or musculoskeletal system, respectively. There was no indication of publication bias. Conclusions The results of this meta-analysis indicate maternal fluoxetine use is associated with a slightly increased risk of cardiovascular malformations in infants. Health care providers and pregnant women must weigh the risk-benefit potential of these drugs when making decisions about whether to treat with fluoxetine during pregnancy. [ABSTRACT FROM AUTHOR]

Aim To perform a meta-analysis of available cohort studies on the association between sertraline use by pregnant women in the first trimester and the findings of congenital anomalies in infants. Methods A comprehensive search of articles published from the index date up to 31st December 2015 investigating the aforementioned associations was conducted on PubMed and Web of Science. Mesh headings used included the terms 'serotonin reuptake inhibitor,' 'sertraline,' 'congenital anomalies' and 'obstetrical outcome.' Results Twelve cohort studies that involved 6 468 241 pregnant women were identified. We summarized odds ratios (ORs) and 95% confidence intervals (CIs) of congenital anomalies using the random-effects model. Pregnant women who used sertraline in the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (OR = 1.36; 95% CI = 1.06-1.74; I2 = 64.4%; n = 12) as well as atrial and/or ventricular septal defects (OR = 1.36, 95% CI = 1.06-1.76; I2 = 62.2%; n = 8). Additionally, positive but nonsignificant associations between sertraline use and congenital anomalies of the nervous system (OR = 1.39; 95% CI = 0.83-2.32; I2 = 0%; n = 5), digestive system (OR = 1.23; 95% CI = 0.76-1.98; I2 = 0%; n = 5), eye, ear, face and neck (OR = 1.08; 95% CI = 0.33-3.55; I2 = 32.1%; n = 3), urogenital system (OR = 1.03; 95% CI = 0.73-1.46; I2 = 0%; n = 5), and musculoskeletal system (OR = 0.97; 95% CI = 0.69-1.36; I2 = 0%; n = 5) were observed. Conclusion This meta-analysis suggested that the use of sertraline use by pregnant women in the first trimester had an increased risk of cardiovascular-related malformations as well as atrial and/or ventricular septal defects in infants. Meanwhile, nonsignificant associations between sertraline use and other congenital anomalies were found. More cohort studies are warranted to provide detailed results of other congenital anomalies. [ABSTRACT FROM AUTHOR]

Selecting plant species that can overcome unfavorable conditions and increase the recovery of degraded mined lands remains a challenge. A pot experiment was conducted to evaluate the feasibility of using transplanted tree seedlings for the phytoremediation of lead/zinc and copper mine tailings. One-year-old bare-root of woody species (Rhus chinensisMill,Quercus acutissimaCarruth,Liquidambar formosanaHance,Vitex trifoliaLinn. var.simplicifoliaCham,Lespedeza cuneataandAmorpha fruticosaLinn) were transplanted into pots with mine tailings and tested as potential metal-tolerant plants. Seedling survival, plant growth, root trait, nutrient uptake, and metal accumulation and translocation were assessed. The six species grew in both tailings and showed different tolerance level.A. fruticosawas highly tolerant of Zn, Pb and Cu, and grew normally in both tailings. Metal concentrations were higher in the roots than in the shoots of the six species. All of the species had low bioconcentration and translocation factor values. However,R. chinensisandL. formosanahad significantly higher translocation factor values for Pb (0.88) and Zn (1.78) than the other species. The nitrogen-fixing species,A. fruticosa,had the highest tolerance and biomass production, implying that it has great potential in the phytoremediation of tailing areas in southern China. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine the potential mechanisms of dietary Zn influencing lipid deposition in yellow catfish Pelteobagrus fulvidraco . For that purpose, yellow catfish were fed three diets containing different Zn levels including 19.82 (adequate Zn), 11.45 (Zn deficiency), 155.97 (Zn excess) mg Zn kg − 1 for 8 weeks, respectively. Lipid and Zn contents, CPT I and LPL activities, and mRNA expression of 12 genes involved in lipid metabolism in the liver and muscle, were determined. As compared to adequate Zn group, excessive dietary Zn apparently reduced lipid content in the liver and muscle, and LPL activity in the muscle, and increased activities of CPT I and LPL in the liver. Dietary Zn deficiency tended to enhance lipid accumulation and CPT I activity in both tissues. Dietary Zn excess increased Zn accumulation in the liver, muscle and whole fish, but dietary Zn deficiency reduced Zn content in the liver and whole fish. In the liver, dietary Zn deficiency significantly down-regulated the transcriptional levels of CPT 1A, PPARα, LepR, G6PD, 6PGD and ACCb, but up-regulated FAS mRNA levels. Dietary Zn excess up-regulated mRNA levels of CPT 1A, PPARα, Lep, LepR, SREBP-1, G6PD, 6PGD, ACCb and LPL, but down-regulated mRNA levels of FAS, ACCa and PPARγ. In the muscle, dietary Zn deficiency down-regulated mRNA levels of PPARα, Lep, SREBP-1, FAS and ACCa, and increased 6PGD and LPL gene expression. Dietary excess Zn down-regulated mRNA levels of PPARγ, SREBP-1, G6PD, ACCa, and LPL, and up-regulated mRNA levels of CPT 1A and Lep. For the first time, our study clearly indicated the different effects of dietary Zn deficiency and excess on lipid deposition and metabolism, which provided new insights into Zn nutrition and toxicology in fish. [ABSTRACT FROM AUTHOR]

The article presents a case study of two Chinese families with dyschromatosis symmetrica hereditaria (DSH) who exhibited pathogenic mutations in the adenosine deaminase acting on RNA 1 (ADAR1) gene. Topics discussed include the amplification of ADAR1 gene through polymerase chain reaction, the amino acid change through the missense mutation, and the genes participating in melanosome synthesis and transport and melanocyte development.

Abstract: Metals such as cadmium and arsenic are ubiquitous toxicants that cause a variety of adverse health effects. Heat shock proteins (HSPs) response to metal-induced stress and protect cells from further damage. However, the intracellular signalling pathways responsible for activation of HSPs expression are not fully understood. Here, we demonstrate that protein phosphatase 2A (PP2A) regulates expression of HSP70 and HSP27 via dephosphorylation of an AMP-activated protein kinase α subunit (AMPKα) at Thr172. Dephosphorylated AMPKα phosphorylates heat shock factor 1 (HSF1) at Ser303, leading to significant transcriptional suppression of HSP70 and HSP27 in CdCl2- or NaAsO2-treated cells. Suppression of PP2A regulatory B56δ subunit resulted in the sustained phosphorylation of AMPKα upon CdCl2 treatment, subsequent reduction in expression of HSP70 and HSP27, and thereby dramatic reduction of reactive oxygen species (ROS) clearance. We further revealed that PP2A B56δ physically interacted with AMPKα, providing evidence that PP2A B56δ–AMPKα–HSF1 signalling pathway participated in regulating the inducible expression of HSPs and ROS clearance. Taken together, we identified a novel PP2A-dependent signalling pathway involved in regulation of HSPs expression in response to metal stress. [Copyright &y& Elsevier]

Abstract: The present study was conducted to determine the effect of dietary Zn deficiency and excess on carnitine status, kinetics and expression of CPT I in the liver and muscle of yellow catfish Pelteobagrus fulvidraco. Yellow catfish were subjected to 20 (adequate Zn), 11.45 (Zn deficiency) and 155(Zn excess)mgkg−1 diet for 8weeks. In the liver, Zn deficiency increased FC, AC and TC contents and did not significantly affect the ratios of FC/TC and AC/FC. Similarly, Zn excess also increased TC and AC contents, and AC/FC ratios, but reduced FC content and FC/TC ratio. In the muscle, FC content was promoted by Zn deficiency and inhibited by Zn excess. FC/TC ratio was stimulated by Zn deficiency and inhibited by Zn excess. In contrast, AC/FC ratio was reduced by Zn deficiency and induced by Zn excess. Zn deficiency also reduced Km and Vmax values while Zn excess increased them in the liver and muscle. Zn deficiency and excess influenced the expression levels of four CPT I isoforms, such as CPT Iα1b, CPT Iβ, CPT Iα2a and CPT Iα1a in the liver and muscle. Furthermore, some correlations were observed in between the expression levels of CPT I isoforms and Km for carnitine, and between CPT I isoform expression and CPT I activity. Thus, for the first time, our study indicated that Zn deficiency and excess showed differential effects on carnitine status, kinetics and expression of CPT I in yellow catfish, which helped provide some novel insights into Zn nutrition and toxicology in fish. [Copyright &y& Elsevier]

Background: Association between parity and colorectal cancer (CRC) risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far. Methods: Relevant published studies of parity and CRC were identified using MEDLINE, EMBASE and Web of Science databases through end of April 2013. Two authors independently assessed eligibility and extracted data. Eleven prospective studies reported relative risk (RR) estimates and 95% confidence intervals (CIs) of CRC risk associated with parity. We pooled the RR from individual studies using fixed- or random-effects models and carried out heterogeneity and publication bias analyses. Results: The summary RR for the ever parity vs. nulliparous was 0.95 (95% CI: 0.88–1.02), with no heterogeneity (Q = 9.04, P = 0.443, I2 = 0.5%). Likewise, no significant association was yielded for the highest vs. lowest parity number (RR = 1.02, 95% CI: 0.89–1.17), with moderate heterogeneity (Q = 17.48, P = 0.094, I2 = 37.1%). Dose-response analysis still indicated no effect of parity on CRC risk and the summary RR of per one livebirth was 0.99 (95% CI: 0.96–1.02), with moderate of heterogeneity (Q = 16.50, P<0.021, I2 = 57.6%). Similar results were observed among all the subgroup analyses. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. Conclusion: Results of this dose-response meta-analysis of prospective studies found that there was little evidence of an association between parity and CRC risk. [ABSTRACT FROM AUTHOR]

Abstract: The present study was conducted to determine dietary zinc (Zn) requirement for juvenile yellow catfish Pelteobagrus fulvidraco and evaluate the effect of dietary Zn levels on growth performance, whole body mineral composition, hepatic intermediary metabolism and antioxidant responses for this fish species. The six experimental diets were formulated to contain the graded levels of ZnSO4·7H2O (0, 0.002, 0.004, 0.008, 0.016 and 0.032%, respectively), providing the actual dietary Zn values of 7.60 (control), 11.90, 16.24, 24.81, 38.75 and 76.36mgkg−1 diet, respectively. Each diet was assigned to three replicate groups of yellow catfish (initial body weight: 6.08±0.12, means±SD) for 8weeks. Increasing dietary Zn level up to 16.24mgkg−1 diet increased growth performance and feed utilization, beyond which they remained nearly unchanged. Whole body lipid contents significantly declined, but whole body moisture and protein contents showed no significant differences with increasing dietary Zn levels. Whole body Zn content tended to increase with increasing dietary Zn level, whereas whole body Cu and Fe contents declined with dietary Zn addition. Hepatic succinate dehydrogenase (SDH), lactate dehydrogenase (LDH) and malic dehydrogenase (MDH) activities showed no significant differences among the treatments. However, lipoprotein lipase (LPL) and hepatic lipase (HL) activities increased with increasing dietary Zn levels. Superoxide dismutase (SOD) activity increased and malondialdehyde (MDA) level declined with increasing dietary Zn levels up to the requirement level. Hepatic catalase (CAT) activity showed no significant differences among the treatments. Analysis by the broken-line regression of specific growth rate (SGR) and protein efficiency rate (PER) indicated that dietary Zn requirements in juvenile yellow catfish were 17.12–20.86mgkg−1 diet. [Copyright &y& Elsevier]

Abstract: Based on the torsion dynamic theory, the method and relative formulae are presented for analyzing the actuating voltage and the switching time, on which the effect of the air squeeze film damping is already considered, for a 2×2 MOEMS optical switch with electrostatic actuating. The computed results show that the switching time will increase markedly under considering the air damping. Furthermore, an optical technique is described for the measurement of the actuating voltage and switching time of the device. Theoretical and experimental results obtained demonstrate the feasibility of the proposed method. The actuating voltage is about 50V, and the switching time Toff and Ton are about 4.8 and 12.5ms, respectively. [Copyright &y& Elsevier]

Short rib-polydactyly syndrome type III (SRPS3) is a lethal perinatal skeletal disorder consisting of polydactyly and multi-system organ abnormalities. To further assess the pathogenicity of two pairs of compound heterozygotes and to search for novel molecular etiology, X-rays and hematoxylin and eosin staining were conducted in three cases: Two retrospective samples and a newly identified patient with SRPS3. In addition, next-generation sequencing was used to evaluate a fetus with SRPS3. Typical radiological features of the three cases included a long, narrow thorax with short ribs, shortened long bones, spurs at the metaphysis of the long bones and congenital bowing of the femurs. The present study also observed atypical histopathological changes, together with the absence of proliferation and abundance of retaining cartilage in the primary spongiosum. In addition, two novel compound heterozygous variants were identified in the dynein cytoplasmic 2 heavy chain 1 (DYNC2H1) gene of the fetus: NM_001080463.1, c.6591_6593delTGG (chr11:103055738-103055740); NM_001080463.1, c.7883T>C (chr11:103070000). The findings of the present study provided further confirmation of the pathogenicity of two compound heterozygous variants in two retrospective samples and identified novel compound heterozygous variants. These findings may improve our knowledge of the histopathological and radiological changes in patients with SRPS3 and the relative effects of DYNC2H1 variants. The findings of the present study may facilitate the clinical and molecular diagnosis of SRPS3. [ABSTRACT FROM AUTHOR]

• Significant estrogenic activities of flavonoid monomers purified from LCC were found. • Molecular docking study confirmed ERs as molecular targets of the flavonoid monomers. • The molecular mechanism was depend on the ERE-independent gene regulation. The main purpose of this study was to evaluate the estrogenic properties of total flavonoids (TFs) and five flavonoid monomers (cardamonin (Car), pinostrobin chalcone (PC), wogonin (Wo), chrysin (Chr) and Pinocembrin (PI)) from leaves of Carya cathayensis Sarg (LCC). TFs from LCC were isolated and determined using HPLC. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were performed to assess the effects of flavonoids on cell proliferation and cell cycle, respectively. The molecular docking technique was applied to investigate binding conformations of the monomers from LCC to the estrogen receptor ERα and ERβ. Gene and protein expression patterns were assessed using quantitative real-time PCR (qRT-PCR) and western blot, respectively. The results showed that TFs, Car, PC, Wo and Chr promoted proliferation of MCF-7 cells and cell transition from the G1 to S phase, and inhabitation of MCF-7 cell proliferation was observed after the treatment of PI. Molecular docking studies confirmed ERs as molecular targets for the monomers. TFs, Car, PC, Wo and Chr from LCC promoted gene expression of ERα, ERβ, progesterone receptor (PR) and pS2. Our collective results demonstrated that TFs and monomers from LCC may exert ER agonist activity through competitively bind to ER, inducing ER upregulation and active ER to estrogen response element (ERE)- independent gene regulation. As an abundant natural product, LCC may provide a novel medicinal source for treatment of diseases caused by estrogen deficiency. [ABSTRACT FROM AUTHOR]

Background: In 2005, the FDA cautioned that exposure to paroxetine, a selective serotonin reuptake inhibitor (SSRI), during the first trimester of pregnancy may increase the risk of cardiac malformations. Since then, the association between maternal use of SSRIs during pregnancy and congenital malformations in infants has been the subject of much discussion and controversy. The aim of this study is to systematically review the associations between SSRIs use during early pregnancy and the risk of congenital malformations, with particular attention to the potential confounding by indication.Methods: The study protocol was registered with PROSPERO (CRD42018088358). Cohort studies on congenital malformations in infants born to mothers with first-trimester exposure to SSRIs were identified via PubMed, Embase, Web of Science, and the Cochrane Library databases through 17 January 2018. Random-effects models were used to calculate summary relative risks (RRs).Results: Twenty-nine cohort studies including 9,085,954 births were identified. Overall, use of SSRIs was associated with an increased risk of overall major congenital anomalies (MCAs, RR 1.11, 95% CI 1.03 to 1.19) and congenital heart defects (CHD, RR 1.24, 95% CI 1.11 to 1.37). No significantly increased risk was observed when restricted to women with a psychiatric diagnosis (MCAs, RR 1.04, 95% CI 0.95 to 1.13; CHD, RR 1.06, 95% CI 0.90 to 1.26). Similar significant associations were observed using maternal citalopram exposure (MCAs, RR 1.20, 95% CI 1.09 to 1.31; CHD, RR 1.24, 95% CI 1.02 to 1.51), fluoxetine (MCAs, RR 1.17, 95% CI 1.07 to 1.28; CHD, 1.30, 95% CI 1.12 to 1.53), and paroxetine (MCAs, RR 1.18, 95% CI 1.05 to 1.32; CHD, RR 1.17, 95% CI 0.97 to 1.41) and analyses restricted to using women with a psychiatric diagnosis were not statistically significant. Sertraline was associated with septal defects (RR 2.69, 95% CI 1.76 to 4.10), atrial septal defects (RR 2.07, 95% CI 1.26 to 3.39), and respiratory system defects (RR 2.65, 95% CI 1.32 to 5.32).Conclusions: The evidence suggests a generally small risk of congenital malformations and argues against a substantial teratogenic effect of SSRIs. Caution is advisable in making decisions about whether to continue or stop treatment with SSRIs during pregnancy. [ABSTRACT FROM AUTHOR]

The relationship between selective serotonin-reuptake inhibitors (SSRIs) use during first trimester and cardiovascular-related malformations of infants is still uncertain. Therefore, we conducted this systematic review and meta-analysis to assess the aforementioned association. A systematic literature review identified studies for cohort studies about SSRIs use and cardiovascular-related malformations in PubMed and Web of Science. We summarized relative risk (RRs) and 95% confidence intervals (CIs) of cardiovascular-related malformations using random-effects model, and heterogeneity and publication-bias analyses were conducted. Eighteen studies met the inclusion criteria. Pregnant women who were exposed to SSRIs at any point during the first trimester had a statistically significant increased risk of infant cardiovascular-related malformations (RR = 1.26, 95%CI = 1.13-1.39), with moderate heterogeneity (I2 = 53.6). The corresponding RR of atrial septal defects (ASD), ventricular septal defects (VSD), ASD and/or VSD was 2.06 (95%CI = 1.40-3.03, I2 = 57.8), 1.15 (95%CI = 0.97-1.36; I2 = 30.3), and 1.27 (95%CI = 1.14-1.42; I2 = 40.0), respectively. No evidence of publication bias and significant heterogeneity between subgroups was detected by meta-regression analyses. In conclusion, SSRIs use of pregnant women during first trimester is associated with an increased risk of cardiovascular-related malformations of infants including septal defects. The safety of SSRIs use during first trimester should be discussed to pregnant women with depression. [ABSTRACT FROM AUTHOR]

We report fabrication and characterization of organic heterojunction UV detectors based on N,N'-bis(naphthalenl-yl)-N,N'-bis (phenyl) benzidine (NPB)and fullerene C60. The effects of different thicknesses of NPB and C60 layers are studied and compared. Notably, the optimal thicknesses of electron acceptor C60 and electron donor NPB are 40 nm and 80 nm, respectively. The J–V characteristic curves of the device demonstrate a three-order-of-magnitude difference when illuminated under a 350 nm UV light and in the dark at −0.5 V. The device exhibits high sensitivity in the region of 320–380 nm with the peak located around 350 nm. Especially, it shows excellent photo-response characteristic with a responsivity as high as 315 mA/W under the illumination of 192 μW·cm−2 350 nm UV light at −5 V. These results indicate that the NPB/C60 heterojunction structure device might be used as low-cost low-voltage UV photodetectors. [ABSTRACT FROM AUTHOR]