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Examines the effects of neurosteroids on GABA receptors in female rats. Demonstration of benzodiazepine insensitivity; Implantation of progesterone capsules to the female rats; Reduction in levels of GABA inhibition.

Purpose: To estimate the time trend in the prevalence of suicidal behaviors including ideation and attempts in Chinese adolescents; to examine the association between suicidal behaviors and overweight (OW)/obesity (OB) and self-perceived weight status., Methods: Data from Youth Risk Behavior Surveys conducted in Ningbo in 2007, 2012, 2017 and 2022 were used for the study. A multistage sampling procedure was used to select respondents aged 12 to 19 years who participated in each survey. Repeated cross-sectional data of anthropometry, weight perception and suicidal behaviors were collected through self-administered questionnaires. A generalized linear model was used to assess associations of ideation and attempts, and weight status and self-perceived weight status., Results: The sample sizes for each survey wave were 937, 889, 1528 and 2655. The prevalence of ideation increased from 11.95% in 2007 to 18.15% in 2022, while the prevalence of attempts remained stable (4.48%-4.26%). An increasing trend in ideation and attempts was found in adolescents who were OW/obese and self-perceived OW/OB from 2007 to 2022. Self-perceived OW/OB adolescents had a significant increase in ideation. Girls had higher likelihood of ideation and attempts for both weight status and self- perceived weight status. While, adolescents aged 12.0-15.9 years had higher odds of ideation than those aged 16.0-19.9 years., Conclusion: Adolescents' self-weight perception, rather than actual weight status, is a critical risk factor of increased likelihood of ideation and attempts in Chinese adolescents. Our findings can support to promote self-esteem growth in school-based health education programmes for prevention of suicidality and psychological health problems., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Weight misperceptions are common in children and adolescents, which is related to the engagement of weight loss behaviors. The aim of this study was to investigate the association between body weight perception and weight loss behaviors of lower-calorie diets and increased levels of physical activity (PA)., Methods: The Ningbo Youth Risk Behavior Survey was conducted from 2007 to 2022. A multistage, stratified cluster sampling procedure was utilized to draw target adolescents aged 12 to 18 years participating in each survey wave (2007, 2012, 2017, 2022). Data of anthropometry, weight perception, and weight loss behaviors were collected through self-administered questionnaires. A binary generalized linear model was used to examine associations between body weight perception and weight loss behaviors of lower calorie diets and increased levels of PA., Results: The sample sizes for each survey wave were 777, 885, 1588 and 2638. The prevalence of overweight (OW)/obesity (OB), self-perception of OW/OB and overestimated perception increased from 7.6%, 27.0% and 29.1% in 2007 to 16.3%, 39.9% and 41.4% in 2022, respectively. Adolescents that perceived themselves as OW/OB had higher odds of lower-calorie diets (OR: 4.2, 3.3-5.4) and increased level of PA (OR: 3.8, 2.9-5.0), whereas adolescents that perceived themselves as underweight had lower odds of lower-calorie diets (OR: 0.371, 0.253-0.542) and increased levels of PA (OR: 0.381, 0.295-0.559)., Conclusion: OW, self-perception of OW/OB and overestimated perception were prevalent in Chinese adolescents. Self-perception of OW/OB was positively associated with lower-calorie diets and increased levels of PA. The results can support public health specialists to promote health education of body perception and improve self-esteem in Chinese children and adolescents., (© 2024. The Author(s).)

Objective: To explore the epidemiological characteristics and spatiotemporal clustering of foodborne infection of Vibrio ( V. ) parahaemolyticus in Ningbo, Zhejiang Province, from 2014 to 2022, and provide reference and evidence for the prevention and control of related diseases. Methods: The incidence data on of foodborne infection of V. parahaemolyticus in Ningbo from 2014 to 2022 were collected from Ningbo Foodborne Disease Surveillance System, and the case counts and the positive rates in different districts (counties, cities) were calculated. Spatial autocorrelation analysis and spatiotemporal scanning analysis were conducted to analyze the spatiotemporal clustering of the diseases. Results: A total of 1 822 cases of foodborne infection of V. parahaemolyticus were reported in Ningbo from 2014 to 2022, with an overall positive rate of 3.78%. Spatial autocorrelation analysis showed that the positive rate of foodborne infection of V. parahaemolyticus in Ningbo was unevenly distributed from 2014 to 2022, Ninghai was a high-high clustering area, while Zhenhai was a high-low clustering area, and Jiangbei was a low-low clustering area. The annual incidence was high during July-September. Spatiotemporal scanning analysis found one class Ⅰ spatiotemporal clustering area and three class Ⅱ spatiotemporal clustering areas, with the class Ⅰ spatiotemporal clustering area being observed in Jiangbei and Zhenhai from 2019 to 2022. Conclusions: Spatiotemporal clustering of foodborne infection of V. parahaemolyticus existed in Ningbo from 2014 to 2022, with an annual high incidence period from July to September. The key areas for the prevention and control of foodborne infection of V. parahaemolyticus are coastal districts (counties, cities) in Ningbo.

Background: Aging is associated with learning and memory disorder, affecting multiple brain areas, especially the hippocampus. Previous studies have demonstrated trilobatin (TLB), as a natural food additive, can extend the life of Caenorhabditis elegans and exhibit neuroprotection in Alzheimer's disease mice. However, the possible significance of TLB in anti-aging remains elusive., Purpose: This study aimed to delve into the physiological mechanism by which TLB ameliorated aging-induced cognitive impairment in senescence-accelerated mouse prone 8 (SAMP8) mice., Methods: 6-month-old SAMP8 mice were administrated with TLB (5, 10, 20 mg/kg/day, i.g.) for 3 months. The therapeutic effect of TLB on aging-induced cognitive impairment was assessed in mice using behavioral tests and aging score. The gut microbiota composition in fecal samples was analyzed by metagenomic analysis. The protective effects of TLB on blood-brain barrier (BBB) and intestinal barrier were detected by transmission electron microscope, H&E staining and western blot (WB) assay. The inhibitive effects of TLB on inflammation in brain and intestine were assessed using immunofluorescence, WB and ELISA assay. Molecular docking and surface plasma resonance (SPR) assay were utilized to investigate interaction between TLB and sirtuin 2 (SIRT2)., Results: Herein, the findings exhibited TLB mitigated aging-induced cognitive impairment, neuron injury and neuroinflammation in hippocampus of aged SAMP8 mice. Moreover, TLB treatment repaired imbalance of gut microbiota in aged SAMP8 mice. Furthermore, TLB alleviated the damage to BBB and intestinal barrier, concomitant with reducing the expression of SIRT2, phosphorylated levels of c-Jun NH2 terminal kinases (JNK) and c-Jun, and expression of MMP9 protein in aged SAMP8 mice. Molecular docking and SPR unveiled TLB combined with SIRT2 and down-regulated SIRT2 protein expression. Mechanistically, the potential mechanism of SIRT2 in TLB that exerted anti-aging effect was validated in vitro. As expected, SIRT2 deficiency attenuated phosphorylated level of JNK in HT22 cells treated with d-galactose., Conclusion: These findings reveal, for the first time, SIRT2-mediated brain-gut barriers contribute to aging and aging-related diseases, and TLB can rescue aging-induced cognitive impairment by targeting SIRT2 and restoring gut microbiota disturbance to mediate the brain-gut axis. Overall, this work extends the potential application of TLB as a natural food additive in aging-related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Fulminant hepatic failure (FHF) lacks efficient therapies notwithstanding increased comprehending of the inflammatory response and oxidative stress play crucial roles in the pathogenesis of this type of hepatic damage. Trilobatin (TLB), a naturally occurring food additive, is endowed with anti-inflammation and antioxidant properties., Purpose: In current study, we evaluated the effect of TLB on FHF with a mouse model with d-galactosamine/lipopolysaccharide (GalN/LPS)-induced FHF and LPS-stimulated Kupffer cells (KCs) injury., Methods: Mice were randomly divided into seven groups: control group, TLB 40 mg/kg + control group, GalN/LPS group, TLB 10 mg/kg + GalN/LPS group, TLB 20 mg/kg + GalN/LPS group, TLB 40 mg/kg + GalN/LPS group, bifendate 150 mg/kg + GalN/LPS group. The mice were administered intragastrically TLB (10, 20 and 40 mg/kg) for 7 days (twice a day) prior to injection of GalN (700 mg/kg)/LPS (100 µg/kg). The KCs were pretreated with TLB (2.5, 5, 10 μM) for 2 h or its analogue (10 μM) or COX2 inhibitor (10 μM), and thereafter challenged by LPS (1 μg/ml) for 24 h., Results: TLB effectively rescued GalN/LPS-induced FHF. Furthermore, TLB inhibited TLR 4/NLRP3/pyroptosis pathway, and caspase 3-dependent apoptosis pathway, along with reducing excessive cellular and mitochondrial ROS generation and enhancing mitochondrial biogenesis. Intriguingly, TLB directly bound to COX2 as reflected by transcriptomics, molecular docking technique and surface plasmon resonance assay. Furthermore, TLB failed to attenuate LPS-induced inflammation and oxidative stress in KCs in the absence of COX2., Conclusion: Our findings discover a novel pharmacological effect of TLB: protecting against FHF-induced pyroptosis and apoptosis through mediating ROS/TLR4/NLRP3 signaling pathway and reducing inflammation and oxidative stress. TLB may be a promising agent with outstanding safety profile to treat FHF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children., Methods: Data from this study was based on 952 schoolchildren (10-12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight., Results: Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity., Conclusions: This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Chronotype has been found to have an important impact on individual's health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Aidi injection (Aidi), a traditional Chinese medicine injection, is often practiced to control malignant pleural effusion (MPE)., Objectives: We performed a registered systematic review and meta-analysis (PROSPERO: CRD42022337611) to clarify the clinical role of Aidi in MPE, reveal optimal combinations of Aidi and chemical agents, their indications, therapeutic route and usage, and demonstrate their clinical effectiveness and safety., Methodology: All randomized controlled trials (RCTs) about Aidi in controlling MPE were collected from Chinese and English databases (up to October 2022). We clustered them into multiple homogenous regimens, evaluated the risk-of-bias at outcome level using a RoB 2, extracted and pooled the data using meta-analysis or descriptive analysis, and finally summarized their evidence quality., Results: All 56 studies were clustered into intrapleural administration with Aidi alone or plus chemical agents, and intravenous administration with Aidi for MPE. Intrapleural administration with Aidi alone displayed similar clinical responses on Cisplatin (DDP) alone. Only administration with Aidi plus DDP significantly improved complete response and quality of life, and displayed a low pleurodesis failure, disease progression, hematotoxicity, gastrointestinal and hepatorenal toxicity. For patients with moderate to massive effusion, Karnofsky Performance Status score ≥ 50 or anticipated survival time ≥3 months, Aidi (50 ml to 80 ml each time, one time each week and three to eight times) plus DDP (20 to 30 mg, 40 to 50 mg, or 60 to 80 mg each time) significantly improved clinical responses. Most results had moderate to low quality., Conclusions: Current evidences indicate that Aidi, a pleurodesis agent, plays an interesting clinical role in controlling MPE. Aidi plus DDP perfusion is a most commonly used regimen, which shows a significant improvement in clinical responses. These findings also provide an indication and possible optimal usage for rational drug use., Competing Interests: Declaration of Competing Interest None of the authors of this manuscript have any financial interest related to this clustered systematic review and meta-analysis., (Copyright © 2023. Published by Elsevier GmbH.)

Background: Existing evidence about associations between change in body mass index (BMI) and waist-to-height ratio (WHtR) change and high blood pressure are relatively limited., Aims: We aimed to investigate the associations of general overweight (based on BMI) and abdominal obesity (based on WHtR) change with high blood pressure in Chinese children., Subjects and Methods: A school-based cohort study in Ningbo region (China) was conducted among children with baseline evaluations in October 2016 with follow-up two years later. A total of 1432 children aged 11-13 years participated in this study., Results: Our results showed that a change from normal BMI or WHtR to overweight or abdominal obesity in children was associated with high blood pressure (adjusted odds ratio (AOR), 2.62; p <0.05 or AOR, 2.79; p <0.05, respectively). In addition, an increased risk of high blood pressure was observed in children who maintained overweight or abdominal obesity (AOR, 1.67; p <0.05 or AOR, 1.69; p <0.05, respectively), but not in children who experienced remission to non-excess weight. Interestingly, children who increased BMI or WHtR had greater impact on SBP than on DBP., Conclusion: The 2-year longitudinal study indicated that general overweight or abdominal obesity can predict the risk factor of high blood pressure in children. However, children who remitted to non-excess weight did not exhibit an increased risk of high blood pressure.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive impairment that currently is uncurable. Previous study shows that trilobatin (TLB), a naturally occurring food additive, exerts neuroprotective effect in experimental models of AD. In the present study we investigated the molecular mechanisms underlying the beneficial effect of TLB on experimental models of AD in vivo and in vitro. APP/PS1 transgenic mice were administered TLB (4, 8 mg· kg -1 ·d -1 , i.g.) for 3 months; rats were subjected to ICV injection of Aβ 25-35 , followed by administration of TLB (2.5, 5, 10 mg· kg -1 ·d -1 , i.g.) for 14 days. We showed that TLB administration significantly and dose-dependently ameliorated the cognitive deficits in the two AD animal models, assessed in open field test, novel object recognition test, Y-maze test and Morris water maze test. Furthermore, TLB administration dose-dependently inhibited microglia and astrocyte activation in the hippocampus of APP/PS1 transgenic mice accompanied by decreased expression of high-mobility group box 1 (HMGB1), TLR4 and NF-κB. In Aβ 25-25 -treated BV2 cells, TLB (12.5-50 μM) concentration-dependently increased the cell viability through inhibiting HMGB1/TLR4/NF-κB signaling pathway. HMGB1 overexpression abrogated the beneficial effects of TLB on BV2 cells after Aβ 25-35 insults. Molecular docking and surface plasmon resonance assay revealed that TLB directly bound to HMGB1 with a K D value of 8.541×10 -4 M. Furthermore, we demonstrated that TLB inhibited Aβ 25-35 -induced acetylation of HMGB1 through activating SIRT3/SOD2 signaling pathway, thereby restoring redox homeostasis and suppressing neuroinflammation. These results, for the first time, unravel a new property of TLB: rescuing cognitive impairment of AD via targeting HMGB1 and activating SIRT3/SOD2 signaling pathway., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Abstract: Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong , and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 μmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 μmol/L), SF (50, 100, 200 μmol/L) group, and N G -nitro-L-arg-methyl ester 1500 μmol/L combined with SF 200 μmol/L or L-arg 1000 μmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and β-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by N G -nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95 %CI ) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status ( HR =1.97,95 %CI 1.38-2.81, P< 0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders ( HR =1.22, 95 %CI 1.08-1.39, P= 0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.

Purpose: This study aimed to examine the association between eating speed and overweight in Chinese schoolchildren., Methods: In all, 664 schoolchildren (10-12 years) from three primary schools participated in this study in China. Their height and body weight were measured. Information about eating speed and other lifestyle behaviors were collected using a self-administered questionnaire. Multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for overweight., Results: Data from 629 students were analyzed. 26.2% of participants reported they were eating fast. The prevalence of overweight (including obesity) was 22.9%, and the mean of sleep duration was 9.69 (SD = 0.63) hours (Table 1). In the multiple linear regression analysis, slower eating speed was independently associated with lower BMI (B = - 0.70, 95% CI - 1.26 to - 0.14) and TG (B = - 0.16, 95% CI - 0.28 to - 0.04). In addition, participants who ate fast were more likely to be overweight (OR 1.81, 95% CI 1.19-2.75) after adjusting for potential confounding factors., Conclusions: This study indicates that eating fast is associated with overweight among Chinese school children., Level of Evidence: Cross-section descriptive study, Level V., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Oxidative stress and aberrant insulin signaling transduction play vital roles in type 2 diabetes mellitus (T2DM). Our previous research has demonstrated that trilobatin (TLB), derived from the leaves of Lithocarpus Polystachyus (Wall.), exhibits a potent antioxidative profile. In the current study, we investigated the anti-T2DM effect of TLB on KK-Ay diabetic mice and further explored the potential mechanisms. Our results showed that TLB significantly reduced the high fasting blood glucose level and insulin resistance and promoted the tolerances to exogenous glucose and insulin in KK-Ay mice. Moreover, TLB reduced the content of reactive oxygen species; enhanced antioxidant enzymes activities, including serum catalase, glutathione peroxidase, and superoxide dismutase; and regulated the abnormal parameters of lipid metabolism, including triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and free fatty acid, as evidenced by enzyme-linked immunosorbent assay. Additionally, TLB markedly ameliorated the pancreatic islet morphology near normal and increased the insulin expression of the islet. Whereafter, TLB promoted Nrf2 that was translocated from cytoplasm to nucleus. Moreover, it increased the protein expressions of HO-1, NQO-1, and GLUT-2, and phosphorylation levels of Akt and GSK-3 β Ser 9 and decreased the protein expressions of keap1 and phosphorylation levels of IRS-1 Ser 307 and GSK-3 β Tyr 216 . Taken together, our findings reveal that TLB exhibits an anti-T2DM effect in KK-Ay mice by activating the Nrf2/ARE signaling pathway and regulating insulin signaling transduction pathway, and TLB is promising to be developed into a novel candidate for the treatment of T2DM in clinic due to its favorable druggability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Zhang, Luo, Xu, Gao, Shi and Gong.)

Inhibition of autophagy has been accepted as a promising therapeutic strategy in cancer, but its clinical application is hindered by lack of effective and specific autophagy inhibitors. We previously identified cepharanthine (CEP) as a novel autophagy inhibitor, which inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. In this study we investigated whether and how inhibition of autophagy/mitophagy by cepharanthine affected the efficacy of chemotherapeutic agent epirubicin in triple negative breast cancer (TNBC) cells in vitro and in vivo. In human breast cancer MDA-MB-231 and BT549 cells, application of CEP (2 μM) greatly enhanced cepharanthine-induced inhibition on cell viability and colony formation. CEP interacted with epirubicin synergistically to induce apoptosis in TNBC cells via the mitochondrial pathway. We demonstrated that co-administration of CEP and epirubicin induced mitochondrial fission in MDA-MB-231 cells, and the production of mitochondrial superoxide was correlated with mitochondrial fission and apoptosis induced by the combination. Moreover, we revealed that co-administration of CEP and epirubicin markedly increased the generation of mitochondrial superoxide, resulting in oxidation of the actin-remodeling protein cofilin, which promoted formation of an intramolecular disulfide bridge between Cys39 and Cys80 as well as Ser3 dephosphorylation, leading to mitochondria translocation of cofilin, thus causing mitochondrial fission and apoptosis. Finally, in mice bearing MDA-MB-231 cell xenografts, co-administration of CEP (12 mg/kg, ip, once every other day for 36 days) greatly enhanced the therapeutic efficacy of epirubicin (2 mg/kg) as compared with administration of either drug alone. Taken together, our results implicate that a combination of cepharanthine with chemotherapeutic agents could represent a novel therapeutic strategy for the treatment of breast cancer., (© 2021. The Author(s).)

Purpose: Little is known about the association between dinner-to-bed time and obesity. Thus, this study was aimed to assess the relationships between dinner-to-bed and overweight/obesity in Chinese school-aged children in Ningbo, China., Methods: Data of this study were based on 1667 schoolchildren (14-15 years) from 14 primary schools participated in this study in China. Anthropometric measurement of height, body weight and waist circumference (WC) was performed. Information about meal duration and other lifestyle behaviors was collected using a self-administered questionnaire. Multivariable logistic regression model was performed to assess the association between dinner-to-bed time and overweight/obesity. Restricted cubic spline regression was drawn to evaluate the shape of the relation between dinner-bed-time and the odds of overweight., Results: Among the study participants, the prevalence of overweight was 17.6%, and the mean of dinner-to-bed time was 4.26 (0.93) h. In the logistic regression analysis, participants who had dinner-to-bed time less than 3 h or 3.01 ~ ≦ 4.00 h are more likely to be overweight (OR = 1.94, 95% CI 1.10-3.42; OR = 1.65, 95% CI 1.03-2.65, respectively) or characterised by abdominal obesity (OR = 3.03, 95% CI 1.86-4.95; OR = 2.61, 95% CI 1.73-3.92, respectively) compared with dinner-to-bed time more than 5 h. In addition, long dinner-to-bed time was associated with lower risks of overweight (OR = 0.83, 95% CI 0.70-0.97) and abdominal obesity (OR = 0.63, 95% CI 0.54-0.73). The cubic spline regression analysis showed that the association between dinner-to-bed time and overweight/abdominal obesity seems to be a linear., Conclusions: This study indicates that short dinner-to-bed time is associated with an increased likelihood of being overweight or characterised by abdominal obesity among Chinese school-aged children., Level of Evidence: Level V; cross-section descriptive study., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Objective: To assess the prevalence of metabolic syndrome (MetS) in Chinese adults living in Ningbo and to examine the association between alcohol consumption and MetS and its medical components., Design: A representative survey in Ningbo was conducted in 2015 covering socio-demography. A FFQ together with additional questionnaires was used to collect information on alcohol consumption, diet, demography, lifestyle and medical information. Multivariable logistic regression and generalised linear models were used to examine the association between alcohol consumption and both MetS and its medical components, respectively., Setting: Ningbo, China., Participants: A total of 2853 adults ≥ 20 years (44 % men) in this final analysis., Results: The prevalence of frequent alcohol drinkers and MetS was 29·9 % and 28·0 %, respectively. Significantly higher prevalence of MetS and mean values of medical components were found in the group of frequent alcohol drinkers with an exception for HDL-cholesterol, compared with less or non-alcohol drinkers. Frequent alcohol consumption was associated with higher odds of developing MetS and positively associated with medical components excepting waist circumference., Conclusions: Frequent alcohol consumption contributed to a higher prevalence of MetS and unfavourable influence on MetS and its medical components among Chinese adults. A public health intervention on alcohol restriction is necessary for the prevention and control of the ongoing epidemic MetS.

Background: Alzheimer's disease (AD) is the most common type of dementia, which brings tremendous burden to the sufferers and society. However, ideal tactics are unavailable for AD. Our previous study has shown that CZ2HF, a Chinese herb preparation, mitigates cognitive impairment in AD rats; whereas, its detailed mechanism has not been elucidated., Methods: Public databases were applied to collect and identify the chemical ingredients of eight herbs in CZ2HF. Criteria of absorption, distribution, metabolism, and excretion was used to screen oral bio-availability and drug-likeness. STITCH database and Therapeutic Target Database were applied to decipher the relationship between compounds and genes related to AD. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology term analyses were used to identify the involved signaling pathways. Cytoscape was adopted to establish the networks The molecular docking was used to validate the interactions between the candidate compounds and their potential targets., Results: 914 compounds were identified in eight herbal medicines of CZ2HF. Among them, 9 compounds and 28 genes were highly involved in the pathologic process of AD. Furthermore, the mechanism of CZ2HF to AD was based on its anti-inflammatory effects mainly through lipopolysaccharide-mediated signaling pathway and TNF signaling pathway. Core genes in this network were TNF, ICAM1, MMP9 and IL-10., Conclusion: This study predicts the active compounds in CZ2HF and uncovers their protein targets using holistic network pharmacology methods. It will provide a insight into the underlying mechanism of CZ2HF to AD from a multi-scale perspective., (© 2021 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University and Wiley‐VCH GmbH.)

Objective: To examine the effect of physical activity (PA) on the incident risk of stroke among adults aged 40 years and above. Methods: The baseline data including PA and demographic characteristics were obtained from the Adult Chronic Disease Surveillance with population representativeness in Ningbo in 2015. The follow-up data of interested health outcomes from 2015 to 2019 were retrieved from a population-based Integrated Noncommunicable Disease Collaborative Management System in Ningbo. The two databases were matched to form a queue. PA was divided into three levels of low-intensity, moderate-intensity, and vigorous-intensity according to the metabolic equivalents (METs) spent per week. Cox regression model was used to calculate the hazard ratio ( HR ) and 95% confidence interval. Results: A total of 3 353 subjects were included at baseline survey in 2015. Until Dec 31, 2019, there had been 31 stroke events had occurred since then, with accumulative incidence rate of 242/100 000, and an average follow-up time of (50.28±2.54) months. When adjusted for gender, age, education level, smoking status, alcohol consumption, BMI and hypertension, multivariate Cox regression analysis showed that greater PA was associated with a 37.9% reduction of incidence of stroke ( HR =0.621,95% CI :0.393-0.983). Compared with those who had low-intensity PA, those who were with vigorous-intensity. PA appeared associated with a 63.1% decrease in the incidence of stroke ( HR =0.369, 95% CI : 0.139-0.976). However, there was no statistical significance with moderate-intensity PA ( HR =0.712,95% CI :0.323-1.569), noticed. Conclusions: Greater PA is likely to reduce the incidence of stroke. Our findings indicated that people should be encouraged to increase the PA level and developing a healthy supportive environment in the community.

Introduction: Aidi injection (Aidi) is composed of cantharidin, astragaloside, ginsenoside, and elentheroside E. As an important adjuvant therapy, Aidi in combination with gemcitabine and cisplatin (GP) is often used in the treatment of non-small cell lung cancer (NSCLC). Objectives: We performed a new evaluation to demonstrate the clinical efficacy and safety of the Aidi and GP combination and further explored an optimal strategy for achieving an ideal response and safety level in advanced NSCLC. Methodology: We collected all the related trials from Chinese and English-language databases, analyzed their methodological bias risk using the Cochrane evaluation Handbook for Systematic Reviews of Interventions Version 5.1.0, extracted all the data using a predefined data extraction form, pooled the data using a series of meta-analyses, and finally summarized the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 70 trials with 5,509 patients. Compared with GP alone, the Aidi and GP combination showed a significant improvement in the objective response rate (ORR) [1.82 (1.62-2.04)], disease control rate (DCR) [2.29 (1.97-2.67)], and quality of life (QOL) [3.03 (2.55-3.60)] and a low incidence of hematotoxicity and gastrointestinal and hepatorenal toxicity. Aidi might be more suitable for patients who are first-treated, elderly, or patients with a Karnofsky Performance Status (KPS) score ≥ 60 or anticipated survival time (AST) ≥3 months. An Aidi (50 ml/day, 7-14 days/cycle for one to two cycles), gemcitabine (1000 mg/m 2 ), and cisplatin (20-30 mg/m 2 , 40-50 mg/m 2 , or 60-80 mg/m 2 ) might be an optimal regimen for realizing an ideal response and safety level. Most results were robust and of moderate quality. Conclusion: Current evidence indicates that Aidi's value in adjuvant chemotherapy may be broad-spectrum, not just for some regimens. The Aidi and GP combination may show a good short-term response, antitumor immunity, and safety level in patients with NSCLC. Aidi (50 ml/day, 7-14 days/cycle for one and two cycles) with GEM (1000 mg/m 2 ) and DDP (20-30 mg/m 2 or 40-50 mg/m 2 ) may be an optimal regimen for realizing an ideal goal in patients who are first-treatment, elderly, or have a KPS score ≥ 60 or AST≥3 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Zheng, Chen, Jiang, Huang, Jiang, Hu, Huang, Liu, Gong, Feng, Xiao, Li and Xiao.)

Trilobatin (TLB) is an effective component from Lithocarpus polystachyrus Rehd. Our previous study revealed that TLB protected against oxidative injury in neuronal cells by AMPK/Nrf2/SIRT3 signaling pathway. However, whether TLB can delay aging remains still a mystery. Therefore, the present study was designed to investigate the possible longevity-enhancing effect of TLB, and further to explore its underlying mechanism in Caenorhabditis elegans ( C. elegans ). The results showed that TLB exerted beneficial effects on C. elegans , as evidenced by survival rate, body movement assay and pharynx-pumping assay. Furthermore, TLB not only significantly decreased ROS and MDA levels, but also increased anti-oxidant enzyme activities including CAT and SOD, as well as its subtypes SOD2 andSOD3, but not affect SOD1 activity, as evidenced by heat and oxidative stress resistance assays. Whereas, the anti-oxidative effects of TLB were almost abolished in SKN1, Sir2.3, and DAF16 mutant C. elegans . Moreover, TLB augmented the fluorescence intensity of DAF16: GFP, SKN1:GFP, GST4:GFP mutants, indicating that TLB increased the contents of SKN1, SIRT3 and DAF16 due to fluorescence intensity of these mutants, which were indicative of these proteins. In addition, TLB markedly increased the protein expressions of SKN1, SIRT3 and DAF16 as evidenced by ELISA assay. However, its longevity-enhancing effect were abolished in DAF16, Sir2.3, SKN1, SOD2, SOD3, and GST4 mutant C. elegans than those of non-TLB treated controls. In conclusion, TLB effectively prolongs lifespan of C. elegans , through regulating redox homeostasis, which is, at least partially, mediated by SKN1/SIRT3/DAF16 signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Li, Shi, Gao, He, Li, Shi and Gong.)

Percutaneous coronary intervention (PCI) is the most widely used therapy for treating ischemic heart disease. However, intimal hyperplasia and restenosis usually occur within months after angioplasty. Modern pharmacological researchers have proven that osthole, the major active coumarin of Cnidium monnieri (L.) Cusson, exerts potent antiproliferative effects in lung cancer cells, the human laryngeal cancer cell line RK33 and TE671 medulloblastoma cells, and its mechanism of action is related to cell cycle arrest. The goal of the present study was to observe the effect of osthole on vascular smooth muscle cell (VSMC) proliferation using platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMCs isolated from rats and vascular balloon injury as models to further elucidate the molecular mechanisms underlying this activity. We detected the relative number of VSMCs by the MTT assay and EdU staining and examined cell cycle progression by flow cytometry. To more deeply probe the mechanisms, the protein expression levels of PCNA, the cyclin D1/CDK4 complex and the cyclin E1/CDK2 complex in balloon-treated rat carotid arteries and the mRNA and protein expression levels of the cyclin D1/CDK4 and cyclin E1/CDK2 complexes in VSMCs were detected by real-time RT-PCR and western blotting. The data showed that osthole significantly inhibited the proliferation of VSMCs induced by PDGF-BB. Furthermore, osthole caused apparent VSMC cycle arrest early in G0/G1 phase and decreased the expression of cyclin D1/CDK4 and cyclin E1/CDK2. Our results demonstrate that osthole can significantly inhibit PDGF-BB-induced VSMC proliferation and that its regulatory effects on cell cycle progression and proliferation may be related to the downregulation of cyclin D1/CDK4 and cyclin E1/CDK2 expression as well as the prevention of cell cycle progression from G0/G1 phase to S phase. The abovementioned mechanism may be responsible for the alleviation of neointimal hyperplasia in balloon-induced arterial wall injury by osthole., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Li, Li, Lv, Gao, Li, Gong and Yang.)

Cerebral ischemia/reperfusion (I/R) results in harmful consequences during ischemic stroke, especially the disruption of the blood-brain barrier (BBB), which leads to severe hemorrhagic transformation through aggravation of edema and brain hemorrhage. Our previous study demonstrated that icariside II (ICS II), which is derived from Herba Epimedii, attenuates cerebral I/R injury by inhibiting the GSK-3β-mediated activation of autophagy both in vitro and in vivo. However, the effect of ICS II on the BBB remains unclear. Thus, in this study, we investigated the regulation of BBB integrity by ICS II after cerebral I/R injury and further explored the underlying mechanism in rats. Cerebral I/R injury was induced by middle cerebral artery occlusion (MCAO), and the treatment groups were administered ICS II at a dose of 16 mg/kg by gavage twice a day for 3 days. The results showed that ICS II effectively prevented BBB disruption, as evidenced by Evans Blue staining. Moreover, ICS II not only significantly reduced the expression of MMP2/9 but also increased TIMP1 and tight junction protein (occludin, claudin 5, and ZO 1) expression. Intriguingly, ICS II may directly bind to both MMP2 and MMP9, as evidenced by molecular docking. In addition, ICS II also inhibited cerebral I/R-induced apoptosis and ameliorated the Bax/Bcl-2 ratio and cleaved-caspase 3 level. Collectively, our findings reveal that ICS II significantly ameliorates I/R-induced BBB disruption and neuronal apoptosis in MCAO rats by regulating the MMP9/TIMP1 balance and inhibiting the caspase 3-dependent apoptosis pathway.

Purpose: This prospectively designed study aimed to investigate the association between sleep duration and overweight in a cohort of Chinese adolescents., Methods: A school-based cohort study with a 2-year follow-up was conducted among Chinese adolescents in Ningbo region (China). For the baseline study, 1901 school-aged Chinese children aged 12-13 years were recruited. Finally, 1510 adolescents were successfully reinterviewed in October 2018. Participants were asked to complete a self-administered questionnaire, and their heights and weights were directly measured., Results: Overweight adolescents had shorter sleep duration or later bedtimes than non-overweight children in baseline (P < 0.05). In the multivariable linear regression analysis, sleep duration was marginally significantly correlated with body mass index (BMI) at baseline and significantly correlated with this parameter at a 2-year follow-up (β = - 0.23, 95% confidence interval (CI): - 0.51 to 0.04, P < 0.1; β = - 0.27, 95% CI: - 0.42 to - 0.11, P < 0.05, respectively). After adjusting for potential confounders, the multivariable logistic regression analysis revealed associations of a longer sleep duration at baseline with a reduced likelihood of participants being overweight both at baseline and at follow-up (adjusted odds ratio (AOR) = 0.81, 95% CI: 0.66 to 1.00, P = 0.05; AOR = 0.43, 95% CI:0.24 to 0.76, P < 0.05, respectively)., Conclusions: Shorter sleep was associated with an increased likelihood of being overweight in Chinese adolescents, while a 1-h decrease in sleep per night led to a more than 50% increase in the overweight risk at the 2-year follow-up.

The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m 2 ) and cisplatin (30-35 mg/m 2 or 40-50 mg/m 2 ) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level., Competing Interests: Declaration of Competing Interest None of the authors of this manuscript have any financial interest related to this meta-analysis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation, and it is also a crucial factor for the development of Alzheimer's disease (AD). Icariside II (ICS II) is an active component isolated from a traditional Chinese herb Epimedium, which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-κB signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and Aβ accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20 μM) or dexamethasone (DXMS, 1 μM) for 1 h, thereafter, treated with LPS for another 24 h. We found that ICS II pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ 1-40 , Aβ 1-42 , amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. Interestingly, molecular docking revealed that ICS II might directly bind to BACE1. It is concluded that ICS II has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD.

Objective: To explore the influence of lifestyle intervention on long-term diabetes in subjects with impaired glucose tolerance (IGT) returned to normal glucose tolerance (NGT) within 6 years. Methods: A total of 577 subjects (aged 25-74 years old) with IGT in Daqing were enrolled and randomly assigned to control, and diet, exercise and diet plus exercise groups in a six-year intervention trial in 1986. Subjects who were non-diabetic at the end of the intervention were followed up for additional 14 years. Results: Among all the subjects, 41.38% of them who had returned to NGT from IGT within 6 years maintained NGT status after 20 years, and had a lower incidence of diabetes than subjects maintained IGT status (46.55% vs. 75.25%). Of note, in the intervention group, the percentage of participants developed diabetes in the NGT subjects was significantly lower than that in the IGT group (43.71% vs. 76.25%) after 20 years. There was high long-term risk for diabetes in the IGT subjects after the adjustment of age, sex and baseline glucose ( HR =1.81, 95 %CI 1.27-2.58, P= 0.001), whereas in the non-intervention group, no significant difference could be viewed in long-term diabetic risk between subjects maintained IGT status and those returned to NGT (71.43% vs. 65.22%) after adjusting of the same confounders ( HR =1.03, 95% CI 0.45-2.35, P= 0.94). Conclusions: IGT subjects who had returned to NGT in early years had lower risk for future diabetes than those who remained IGT. However, this beneficial effect could only be viewed in the intervention group, but not in the non-intervention group.

Sodium ferulate (SF) is the sodium salt of ferulic acid which is an active ingredient of Radix Angelica Sinensis and Ligusticum chuanxiong hort. Here, we investigated SF inhibition in a rat model of myocardial hypertrophy induced by coarctation of the abdominal aorta. Following coarctation, rats were given SF (20, 40, and 80 mg/kg/day) for 25 consecutive days. We characterized myocardial hypertrophy using myocardial hypertrophic parameters, histopathology, and gene expression of atrial natriuretic factor (ANF) -a gene related to myocardial hypertrophy. We detected the levels of angiotensin II (Ang II) and endothelin-1 (ET-1), protein kinase C beta (PKC-β), Raf-1, extracellular regulated protein kinase 1/2 (ERK1/2), and mitogen-activated protein kinase phosphatase-1 (MKP-1) in myocardium. Notably, coarctation of the abdominal aorta increases myocardial hypertrophic parameters, cardiac myocyte diameter, the concentration of Ang II and ET-1 in myocardium, and gene expression of ANF. SF significantly ameliorates myocardial hypertrophy caused by coarctation of the abdominal aorta; reduces concentrations of Ang II and ET-1; suppresses the overexpression of ANF, PKC-β, Raf-1, and ERK1/2; and increases the expression of MKP-1. These results indicate that SF alleviates myocardial hypertrophy induced by coarctation of the abdominal aorta, and these protective effects could be related to the inhibition of PKC and mitogen-activated protein kinase (MAPK) signaling pathways., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To examine the association between 25-Hydroxyvitamin D (25(OH)D) levels and sleep duration among Chinese adolescents., Subjects and Methods: A school-based cross-sectional study was conducted among Chinese adolescents in 2017. Data on a total of 800 adolescents aged 8⁻14 years was used for this study. Anthropometric measurements such as height and weight were measured by trained research staff. Serum 25(OH)D and lipids were measured in the laboratory. Sleep habits and other health-related behaviors were tested by questionnaire., Results: 25(OH)D levels were significantly positively correlated with sleep duration ( r = 0.11, p < 0.05). In multivariate logistic regression analyses, insufficiency/deficiency of vitamin D (25(OH)D ≤ 20 ng/mL) was significantly associated with increased probability of short sleep (AOR = 1.67, 95% CI = 1.14⁻2.43)., Conclusions: Low 25(OH)D levels were independently associated with the risk of insufficient sleep in Chinese adolescents.

Objectives: The objective of this study was to investigate the relationship between sleep duration and overweight/obesity among Chinese adolescents., Methods: A school-based cross-sectional study was conducted among Chinese adolescents in 2016. In total, 2795 school-aged Chinese children aged 12 to 13 years participated in this study. Participants were asked to complete self-administered surveys during a 45-min class period in their classroom. Details of the questionnaire about health-related behaviors included sleep habits, physical activity, screen time, cigarette use, and alcohol use. Height, weight, waist circumference and hip circumference were directly measured., Results: The mean sleep duration was 8.7 h/day. In total, 43.0% of the participants had a sleep duration of less than 9 h/day. Sleep duration was significantly inversely related to BMI, waist circumference, hip circumference and WHtR in multiple linear regression analyses in both genders. Logistic regression models showed that insufficient sleep (<9 h/day) was associated with high odds of overweight/obesity among both young boys and girls., Conclusions: Insufficient sleep duration was associated with overweight/obesity in Chinese adolescents, and short sleep duration was probably associated with central adiposity, especially among boys., Competing Interests: The author declared no conflict of interest.

Objective: To investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms., Methods: Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca 2+ ] i ) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively. The mRNA expressions of atrial natriuretic factor (ANF), calcineurin (CaN), extracellular signal-regulated kinase-2 (ERK-2), and endothelial nitric oxide synthase (eNOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit (CnA) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by Western blot analysis., Results: Compared with the control group, Ang II induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF mRNA expression; increased intracellular free calcium ([Ca 2+ ] i ) concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but decreased MKP-1 protein expression (P<0.05 or P<0.01). Compared with Ang II, Evo (0.3, 3 μmol/L) significantly attenuated Ang II-induced cardiomyocyte hypertrophy, decreased the [Ca 2+ ] i concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but increased MKP-1 protein expression (P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the eNOS mRNA expression (P<0.05)., Conclusion: Evo signifificantly attenuated Ang II-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca 2+ ]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.

Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin-Eosin staining. Flow cytometry was used for evaluating apoptosis in the hippocampi. The target protein expression was examined by Western blot. The results showed that BCCAO induced cognitive impairment, hippocampus CA1 and CA3 pyramidal neuron damage, beta-amyloid (Aβ) deposition, excessive autophagy, and apoptosis. GAS treatment significantly improved BCCAO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that GAS exerted the protective effect via reducing the levels of Aβ1-40/42, APP, and β-site APP-cleaving enzyme 1 expression, and increasing Aβ-related protein, a disintegrin and metalloprotease 10, and insulin degrading enzyme expression. Meanwhile, GAS inhibited excessive autophagy via decreasing Beclin-1, LC3-II, and p62 levels. Furthermore, GAS inhibited apoptosis through the downregulation of Bax and upregulation of Bcl-2. Moreover, P38 MAPK signaling pathway was involved in the process. Our findings demonstrate that GAS was effective in the treatment of BCCAO-induced VD via targeting Aβ-related protein formation and inhibiting autophagy and apoptosis of hippocampus neurons.

Objective: To assess the association between sleep duration and physical activity and dietary behaviors among adolescents in a representative sample., Methods: The analysis was performed using data from the 2015 Ningbo Youth Risk Behavior Survey. Associations between physical activity and dietary behaviors and sleep duration were examined on weighted data using logistic regression., Results: Of the 10726 students, roughly 40% reported sleep duration <8 h. Longer sleep duration was associated with higher likelihood of milk intake, fruit consumption, vegetable consumption, water consumption, moderate physical activity, and muscle-strengthening physical activity, and with a lower likelihood of cigarette use, alcohol use, sweets intake, Western fast food intake, and breakfast skipping., Conclusion: Insufficient sleep may be common among Chinese adolescents. Sleep duration was associated with dietary behaviors, physical activity, and other health-related behaviors. These findings suggest that sleep duration could be a potential target for many health-risk behaviors in young adolescents., (Copyright © 2017. Published by Elsevier B.V.)

Dendrobium nobile Lindl. alkaloids (DNLA), the active ingredients of a traditional Chinese medicine Dendrobium , have been shown to have anti-oxidative effects, anti-inflammatory action, and protective effect on neurons against oxygen-glucose deprivation. However, it is not clear whether DNLA reduces amyloid-beta (Aβ)-induced neuronal injury. In this study, cortical neurons were treated with DNLA at different concentrations (0.025, 0.25, and 2.5 mg/L) for 24 hours, followed by administration of Aβ 25-35 (10 μM). Aβ 25-35 treatments increased cell injury as determined by the leakage of lactate dehydrogenase, which was accompanied by chromatin condensation and mitochondrial tumefaction. The damage caused by Aβ 25-35 on these cellular properties was markedly attenuated when cells were pretreated with DNLA. Treatment with Aβ 25-35 down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95, all changes were significantly reduced by pretreatment of cells with DNLA. These findings suggest that DNLA reduces the cytotoxicity induced by Aβ 25-35 in rat primary cultured neurons. The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated, at least in part, through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95., Competing Interests: Conflicts of interest: None declared.

Aims: Axonal degeneration is a pathological symbol in the early stage of Alzheimer's disease (AD), which can be triggered by amyloid-β (Aβ) peptide deposition. Growing evidence indicates that deficit of autophagy eventually leads to the axonal degeneration. Our previous studies have shown that Dendrobium nobile Lindl alkaloid (DNLA) had protective effect on neuron impairment in vivo and in vitro; however, the underlying mechanisms is still unclear., Methods: We exposed cultured hippocampus neurons to Aβ 25-35 to investigate the effect of DNLA in vitro. Axonal degeneration was evaluated by immunofluorescence staining and MTT assay. Neurons overexpressing GFP-LC3B were used to measure the formation of autophagosome. Autophagosome-lysosome fusion, the lysosomal pH, and cathepsin activity were assessed to reflect autophagy process. Proteins of interest were analyzed by Western blot., Results: DNLA pretreatment significantly inhibited axonal degeneration induced by Aβ 25-35 peptide in vitro. Further studies revealed DNLA treatment increased autophagic flux through promoting formation and degradation of autophagosome in hippocampus neurons. Moreover, enhancement of autophagic flux was responsible for the protective effects of DNLA on axonal degeneration., Conclusions: DNLA prevents Aβ 25-35 -induced axonal degeneration via activation of autophagy process and could be a novel therapeutic target., (© 2017 John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is known to be caused by the accumulation of amyloid-β peptide (Aβ). The accumulation of Aβ has been shown to cause learning and memory impairment in rats, and it has been shown that hydrogen sulfide donors, such as sodium hydrosulfide (NaHS) can attenuate these effects. However, the underlying mechanisms have not yet been fully eludicated. This study was designed to investigate whether NaHS attenuates the inflammation and apoptosis induced by Aβ. We demonstrated that NaHS attenuated Aβ25‑35-induced neuronal reduction and apoptosis, and inhibited the activation of pro-caspase-3. It also decreased the protein expresion of phosphodiesterase 5 (PDE5) in the hippocampus of the rats. In addition, NaHS upregulated the expression of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ, but it did not affect the expression of PPAR-β. Moreover, the Aβ25‑35‑exposed rats exhibited a decrease in IκB-α degradation and an increase in nuclear factor-κB (NF-κB) p65 phosphorylation levels, whereas these effects were attenuated by NaHS. Our data suggest that NaHS prevents Aβ-induced neurotoxicity via the upregulation of PPAR-α and PPAR-γ and the inhibition of PDE5. Hence NaHS may prove to be beneficial in the treatment of AD.

Icariin (ICA), an active component of Epimedium brevicornum Maxim, exerts a variety of neuroprotective effects such as antiapoptosis. However, the mechanisms underlying antiapoptosis of ICA in neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) are unclear. The B-cell lymphoma-2 (Bcl-2) protein family plays an important role in the regulation of apoptosis and autophagy through Bcl-2-dependent cross talk. Bcl-2 suppresses apoptosis by binding to Bax and inhibits autophagy by binding to Beclin-1 which is an autophagy related protein. In the present study, MTT result showed that ICA increased cell viability significantly in OGD/R treated PC12 cells (P < 0.01). Results of western blotting analysis showed that ICA increased Bcl-2 expression significantly and decreased expressions of Bax, cleaved Caspase-3, Beclin-1, and LC3-II significantly in OGD/R treated PC12 cells (P < 0.01). These results suggest that ICA protects PC12 cells from OGD/R induced autophagy via Bcl-2-dependent cross talk between apoptosis and autophagy.

Multipartite quantum entanglement is a key resource for ensuring security in quantum network. We show that by using a unified parameter in terms of reduced noise variances one can determine different types of tripartite entanglement of a given state generated in a hybrid optomechanical system, where an atomic ensemble is located inside a single-mode cavity with a movable mirror, with different thresholds for each type. In particular, the special quantum states which allow both entanglement and steering genuinely shared among atom-light-mirror modes can be observed, even though there is no direct interaction between the mirror and the atomic ensemble. We further show the robustness against mechanical thermal noise and damping, the relaxation time of atomic ensemble, as well as the effect of gain factors involved in the criteria. Our analysis provides an experimentally achievable method to determine the type of tripartite quantum correlation in a way.

Chronic cerebral hypoperfusion is considered to be a pivotal contributing factor of cognitive impairments that occur in vascular dementia and Alzheimer's disease, and ideal drug treatment for these diseases is unavailable. Hence, this study was designed to investigate the protective effects of icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum, on cognitive impairments and neuronal morphological damage induced by permanent occlusion of bilateral common carotid arteries (BCCAO) in rats, and further explore the potential mechanisms. This study found that BCCAO could induce cognitive deficits and neuronal morphological damage, along with deposition of beta-amyloid (Aβ) in rat hippocampus. However, oral administration of icariin twice per day for 23days might attenuate cognitive deficits and neuronal morphological damage induced by BCCAO. Subsequently, icariin decreased the level of Aβ in rat hippocampus subjected to BCCAO. Administration of icariin reduced the expressions of amyloid precursor protein (APP), beta-secretase 1 (BACE1), and increased the expressions of insulin-degrading enzyme (IDE) and a disintegrin and metalloproteinase domain 10 (ADAM10) in rat hippocampus. Furthermore, icariin afforded beneficial actions in suppressing transforming growth factor-β1 (TGF-β1) signaling via inhibition of Smad2/3 phosphorylation. In summary, icariin is effective in improving cognitive deficits and hippocampus morphological alterations subjected to BCCAO. This protection appears to be due to the decreased expressions of both APP and BACE1, and the increased expressions of both IDE and ADAM10, resulting in a decrease in the level of insoluble Aβ fragments in rat hippocampus. Inhibitions of TGF-β1 signaling and Smad2/3 phosphorylation are involved in the course., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Fluctuations in circulating levels of ovarian hormones have been shown to regulate cognition (Sherwin and Grigorova, 2011. Fertil. Steril. 96, 399-403; Shumaker et al., 2004. JAMA. 291, 2947-2958), but increases in estradiol on the day of proestrus yield diverse outcomes: In vivo induction of long-term potentiation (LTP), a model of learning, is reduced in the morning, but optimal in the afternoon (Warren et al., 1995. Brain Res. 703, 26-30). The mechanism underlying this discrepancy is not known. Here, we show that impairments in both CA1 hippocampal LTP and spatial learning observed on the morning of proestrus are due to increased dendritic expression of α4βδ GABAA receptors (GABARs) on CA1 pyramidal cells, as assessed by electron microscopic (EM) techniques, compared with estrus and diestrus. LTP induction and spatial learning were robust, however, when assessed on the morning of proestrus in α4-/- mice, implicating these receptors in mediating impaired plasticity. Although α4βδ expression remained elevated on the afternoon of proestrus, increases in 3α-OH-THP (3α-OH-5α-pregnan-20-one) decreased inhibition by reducing outward current through α4βδ GABARs (Shen et al., 2007. Nat. Neurosci. 10, 469-477), in contrast to the usual effect of this steroid to enhance inhibition. Proestrous levels of 3α-OH-THP reversed the deficits in LTP and spatial learning, an effect prevented by the inactive metabolite 3β-OH-THP (10 mg/kg, i.p.), which antagonizes actions of 3α-OH-THP. In contrast, administration of 3α-OH-THP (10 mg/kg, i.p.) on the morning of proestrus improved spatial learning scores 150-300%. These findings suggest that cyclic fluctuations in ovarian steroids can induce changes in cognition via α4βδ GABARs that are dependent upon 3α-OH-THP. This article is part of a Special Issue entitled SI: Brain and Memory., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Icariin is derived most commonly from the traditional Chinese herb Epimedium brevicornum Maxim. Our previous studies have shown that icariin protects neurons from neurotoxic and ischemic conditions. This study aims to investigate the effect of icariin on the expression of amyloid precursor protein (APP) and the level of amyloid-β peptide (Aβ), as well as neurogenesis in the brain of Tg2576 mice, an animal model of Alzheimer's disease (AD). Tg2576 mice and wild-type littermates (WT) were randomized into the following three groups: Tg2576, Tg2576+icariin, and WT groups. All 9-month-old mice were treated with icariin (60mg/kg/d) or distilled water for 3months. Following this, the spatial working memory of Tg2576+icariin mice, as examined in the Y-maze task, was found to improve. Furthermore, reduced levels of insoluble Aβ1-40 (69%) and Aβ1-42 (50%) after icariin treatment were determined in the brain by enzyme-linked immunosorbent assay (ELISA). Western blot analysis indicated the downregulation of APP expression after icariin treatment, and double staining showed an increased number of 5-bromo-2-deoxyuridine (BrdU)/Neuron-specific nuclear protein (NeuN) double-positive cells in the dentate gyrus region of the hippocampus in Tg2576+icariin mice compared with the Tg2576 mice. The current study demonstrated that icariin improved memory function, decreased the levels of Aβ and APP in the brain, and enhanced neurogenesis in the hippocampus of Tg2576 mice. Collectively, these results suggest the potential therapeutic value of icariin in AD., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

A practical scheme for the demonstration of perfect one-sided device-independent quantum secret sharing is proposed. The scheme involves a three-mode optomechanical system in which a pair of independent cavity modes is driven by short laser pulses and interact with a movable mirror. We demonstrate that by tuning the laser frequency to the blue (anti-Stokes) sideband of the average frequency of the cavity modes, the modes become mutually coherent and then may collectively steer the mirror mode to a perfect Einstein-Podolsky-Rosen state. The scheme is shown to be experimentally feasible, it is robust against the frequency difference between the modes, mechanical thermal noise and damping, and coupling strengths of the cavity modes to the mirror.

Two pillared-layer metal-organic frameworks (MOFs; PMOF-55 and NH2 -PMOF-55) based on 1,2,4-triazole and terephthalic acid (bdc)/NH2 -bdc ligands were assembled and display framework stabilities, to a certain degree, in both acid/alkaline solutions and toward water. They exhibit high CO2 uptakes and selective CO2 /N2 adsorption capacities, with CO2 /N2 selectivity in the range of 24-27, as calculated by the ideal adsorbed solution theory method. More remarkably, the site and interactions between the host network and the CO2 molecules were investigated by single-crystal X-ray diffraction, which showed that the main interaction between the CO2 molecules and PMOF-55 is due to multipoint supramolecular interactions of C-H⋅⋅⋅O, C⋅⋅⋅O, and O⋅⋅⋅O. Amino functional groups were shown to enhance the CO2 adsorption and identified as strong adsorption sites for CO2 by X-ray crystallography., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Previous studies have demonstrated that DNA damage induces atherosclerosis and that oxidative stress has an important role in DNA damage. Gypenosides (Gps), the main ingredient of Gynostemma Pentaphylla (Thunb.) Makino, have been recognized as specific antioxidants and have previously been reported to inhibit high‑fat diet‑induced atherosclerosis in rats. However, whether or not Gps attenuate DNA damage through their antioxidant effects remains to be elucidated. The current study was performed to clarify whether or not Gps can inhibit cholesterol‑induced DNA damage through antioxidation. The present study provided new insights into the pharmacological effects of Gps on atherosclerosis. HUVECs were treated with Gps at various concentrations (1, 10 and 100 µg/ml) for 1 h. The protective effects of Gps on cholesterol‑induced DNA damage were determined using immunofluorescence, western blotting, reverse‑transcription quantitative polymerase chain reaction and flow cytometry. Pretreatment with Gps (1, 10 and 100 µg/ml) effectively attenuated cholesterol‑induced DNA damage in HUVECs by inhibiting phosphorylation of H2AX, a member of the histone family. Furthermore, Gps (100 µg/ml) pretreatment inhibited cholesterol‑induced transcription and activity of nicotinamide adenine dinucleotide phosphate‑oxidase 4 and reduced intracellular ROS levels. In conclusion, Gps attenuated cholesterol‑induced DNA damage by inhibiting ROS production in HUVECs, suggesting that the inhibitory effect of Gps on atherogenesis is correlated with the alleviation of DNA damage.

Using Venn diagrams, we classify the different types of two-mode Gaussian continuous variable quantum correlation including directional entanglement and Einstein-Podolsky-Rosen (EPR) steering. We establish unified signatures for one- and two-way quantum steering, entanglement, and discord beyond entanglement in terms of an EPR-type variance. By focusing on Gaussian states, we link an optimized condition for entanglement based on an EPR variance to the Simon-Peres condition. This allows us to quantify the asymmetry of the Gaussian entanglement, and to relate the asymmetry to a directional quantum teleportation protocol where Alice and Bob possess asymmetrically noisy channels. Our analysis enables a determination of the type and direction of quantum correlation in a way that is easily measured in experiment. We also find that for symmetric states, when discord exceeds a certain threshold, the states are necessarily steerable.

Objective: Previous meta-analyses have demonstrated that lifestyle modification can reduce the blood glucose levels in patients with type 2 diabetes, although the effects of changes in the blood glucose level on impaired glucose tolerance (IGT) remain controversial. This review therefore aimed to determine the efficacy of lifestyle interventions in adults with IGT., Methods: We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Two independent reviewers extracted the data and assessed the quality of the included studies; a total of nine randomized controlled trials met the inclusion criteria. In addition, we tested for trial heterogeneity and calculated the pooled effects size using the random effects model., Results: The overall interventions were associated with a decline in the 2-hour plasma glucose levels [standardized mean differences (SMD) -0.56; 95% confidence interval (CI), -1.01 to -0.10; I(2), 96.6%]. Moreover, dietary intervention (SMD -0.53; 95% CI -0.77 to -0.28) and physical intervention (SMD -0.42; 95% CI -0.63 to -0.20) were each associated with a decline in the 2-hour plasma glucose levels compared with that observed in the control participants. The overall interventions were associated with a decline in the fasting plasma glucose (FPG) levels (SMD -0.27; 95% CI -0.38 to -0.15; I(2) = 47.1%). In addition, physical intervention (SMD -0.25; 95% CI -0.44 to -0.05) and combined dietary and physical intervention were each associated with a decreased FPG level (SMD -0.28; 95% CI -0.44 to -0.12) compared with that observed in the control participants., Conclusion: Lifestyle modification based on physical or dietary interventions or both is associated with improvements in the 2-hour plasma glucose and FPG levels in IGT patients.

Well-ordered silicon nanowires (SiNWs) are applied as surface-enhanced Raman scattering (SERS) substrates. Laser interference lithography is used to fabricate large-area periodic nanostructures. By controlling the reaction time of metal assisted chemical etching, various aspect ratios of SiNWs are generated. Ag nanoparticles are decorated on the substrates via redox reaction to allow a good coverage of Ag over the SiNWs. As the height of the SiNWs increases, the light scattering inside the structures is enhanced. The number of the probing molecules within the detection volume is increased as well. These factors contribute to stronger light-matter interaction and thus lead to higher SERS signal intensity. However, the light trapping effect is more significant for higher SiNWs, which prevents the detection of the SERS signals. An optimized aspect ratio ∼5:1 (1 μm height and 200 nm width) for the SiNW array is found. The well-ordered SiNWs demonstrate better SERS signal intensity and uniformity than the randomly arranged SiNWs.