Interleukin-21 receptor signaling promotes metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma by inducing immunosuppressive IgA+ B cells.

BACKGROUND: Dysregulation of immune surveillance is tightly linked to the development of metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC); however, its underlying mechanisms remain unclear. Herein, we aimed to determine the role of interleukin-21 receptor (IL-21R) in MASH-driven HCC. METHODS: The clinical significance of IL-21R was assessed in human HCC specimens using immunohistochemistry staining. Furthermore, the expression of IL-21R in mice was assessed in the STAM model. Thereafter, two different MASH-driven HCC mouse models were applied between IL-21R-deficient mice and wild type controls to explore the role of IL-21R in MASH-driven HCC. To further elucidate the potential mechanisms by which IL-21R affected MASH-driven HCC, whole transcriptome sequencing, flow cytometry and adoptive lymphocyte transfer were performed. Finally, flow cytometry, enzyme-linked immunosorbent assay, immunofluorescent staining, chromatin immunoprecipitation assay and western blotting were conducted to explore the mechanism by which IL-21R induced IgA+ B cells. RESULTS: HCC patients with high IL-21R expression exhibited poor relapse-free survival, advanced TNM stage and severe steatosis. Additionally, IL-21R was demonstrated to be upregulated in mouse liver tumors. Particularly, ablation of IL-21R impeded MASH-driven hepatocarcinogenesis with dramatically reduction of lipid accumulation. Moreover, cytotoxic CD8+ T lymphocyte activation was enhanced in the absence of IL-21R due to the reduction of immunosuppressive IgA+ B cells. Mechanistically, the IL-21R-STAT1-c-Jun/c-Fos regulatory axis was activated in MASH-driven HCC and thus promoted the transcription of Igha, resulting in the induction of IgA+ B cells. CONCLUSIONS: IL-21R plays a cancer-promoting role by inducing IgA+ B cells in MASH-driven hepatocarcinogenesis. Targeting IL-21R signaling represents a potential therapeutic strategy for cancer therapy.

Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.

Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE. A bipolar electrode was implanted into hippocampal CA3 in male mice for kindling stimulation and EEG recording; a special promoter with enhanced synaptic activity-responsive element (E-SARE) was used to label seizure-activated neurons in the subiculum; the activity of subicular seizure-activated neurons was manipulated using chemogenetic approach; cognitive function was assessed in object location memory (OLM) and novel object recognition (NOR) tasks. We showed that chemogenetic inhibition of subicular seizure-activated neurons (mainly CaMKIIα+ glutamatergic neurons) alleviated seizure generalization and improved cognitive performance, but inhibition of seizure-activated GABAergic interneurons had no effect on seizure and cognition. For comparison, inhibition of the whole subicular CaMKIIα+ neuron impaired cognitive function in naïve mice in basal condition. Notably, chemogenetic inhibition of subicular seizure-activated neurons enhanced the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks. Our results demonstrate that subicular seizure-activated neurons contribute to cognitive impairment in TLE, suggesting seizure-activated neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

UPLC-QE-Orbitrap-Based Cell Metabolomics and Network Pharmacology to Reveal the Mechanism of N-Benzylhexadecanamide Isolated from Maca (Lepidium meyenii Walp.) against Testicular Dysfunction.

Testicular dysfunction (TDF) is characterized by testosterone deficiency and is caused by oxidative stress injury in Leydig cells. A natural fatty amide named N-benzylhexadecanamide (NBH), derived from cruciferous maca, has been shown to promote testosterone production. Our study aims to reveal the anti-TDF effect of NBH and explore its potential mechanism in vitro. This study examined the effects of H2O2 on cell viability and testosterone levels in mouse Leydig cells (TM3) under oxidative stress. In addition, cell metabolomics analysis based on UPLC-Q-Exactive-MS/MS showed that NBH was mainly involved in arginine biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, the TCA cycle and other metabolic pathways by affecting 23 differential metabolites, including arginine and phenylalanine. Furthermore, we also performed network pharmacological analysis to observe the key protein targets in NBH treatment. The results showed that its role was to up-regulate ALOX5, down-regulate CYP1A2, and play a role in promoting testicular activity by participating in the steroid hormone biosynthesis pathway. In summary, our study not only provides new insights into the biochemical mechanisms of natural compounds in the treatment of TDF, but also provides a research strategy that integrates cell metabolomics and network pharmacology in order to promote the screening of new drugs for the treatment of TDF.

Diagnostic value of Lipoarabinomannan antigen for detecting Mycobacterium tuberculosis in adults and children with or without HIV infection.

OBJECTIVES: Even today, tuberculosis (TB) remains a leading public health problem; yet, the current diagnostic methods still have a few shortcomings. Lipoarabinomannan (LAM) provides an opportunity for TB diagnosis, and urine LAM detection seems to have a promising and widely applicable prospect. DESIGN OR METHODS: Four databases were systematically searched for eligible studies, and the quality of the studies was evaluated using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2). Graphs and tables were created to show sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), the area under the curve (AUC), and so on. RESULTS: Based on the included 67 studies, the pooled sensitivity of urine LAM was 48% and specificity was 89%. In the subgroup analyses, the FujiLAM test had higher sensitivity (69%) and specificity (92%). Furthermore, among patients infected with human immunodeficiency virus (HIV), 50% of TB patients were diagnosed using a urine LAM test. Besides, the CD4+ cell count was inversely proportional to the sensitivity. CONCLUSIONS: Urine LAM is a promising diagnostic test for TB, particularly using the FujiLAM in HIV-infected adults whose CD4+ cell count is ≤100 per µl. Besides, the urine LAM test shows various sensitivities and specificities in different subgroups in terms of age, HIV infection status, CD4+ cell count, and testing method.

Prevalence of myopia and influencing factors among high school students in Nantong, China: A cross-sectional study.

INTRODUCTION: Myopia is an increasingly serious health problem in China. The aim of this study was to investigate the prevalence of myopia and the factors associated with it among students in Nantong, China, to show the current status of myopia prevention. METHODS: This school-based, cross-sectional study examined students from all high schools in an urban area of Nantong, China. At least two classes were randomly selected from each grade of each school. A self-reported questionnaire was used to collect the required information.Univariate analyses were performed to identify associations between myopia and various parameters.Non-cycloplegic autorefraction and visual acuity were assessed for each student. Factors that were statistically significant in univariate analyses were selected for multivariate analyses. Myopia was defined as a spherical equivalent refraction of ≤ -0.5 diopters. RESULTS: The completion percentage of students out of the whole high school was 6.5%.The overall prevalence of myopia was 94%. The response percentage of the number of validated questionnaires was 90.2%, of which 50.2% (n = 1,466) were from male participants, and 49.8% (n = 1,452) were from female participants. The mean (SD) of age was 15.22±1.75 years, ranging from 12-18 years. Factors such as female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia (P < 0.05). In the myopic population, most students (67.9%) did not take measures to prevent further progression of myopia. CONCLUSION: The prevalence of myopia among high school students was 94%. Female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia. Most students with myopia (67.9%) did not take measures to prevent further progression of myopia.

Liraglutide Attenuates Restenosis After Vascular Injury in Rabbits With Diabetes Via the TGF-ß/Smad3 Signaling Pathway.

Background: Lower limb ischemia due to arterial stenosis is a major complication in patients with diabetes mellitus (DM). Liraglutide is a long-acting analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist used for lowering blood glucose in patients with DM, and is believed to possess cardiovascular protective effects. The aim of this study was to investigate whether liraglutide has a protective effect on blood vessels and alleviates vascular intimal hyperplasia in streptozotocin (STZ)-induced rabbits with DM and its molecular mechanism. Methods: Rabbits with DM were induced by STZ, and a lower limb ischemia model was established. The animals were divided into a control group, DM-injury group and liraglutide treatment group. Pathological staining was used to observe the intimal growth, analyze the oxidation levels of malondialdehyde (MDA), superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px), and analyze the changes in expression of marker proteins and signaling pathway proteins by Western blotting. A hyperglycemia (HG)-injured vascular smooth muscle cells (VSMCs) model was established to analyze reactive oxygen species (ROS) levels, Cell-Counting Kit-8 (CCK-8) was used to analyze cell proliferation, scratch assay and Transwell Migration Assay to analyze cell migration, flow cytometry to analyze apoptosis and Western blotting was used to analyze changes in the expression of marker and signaling pathway proteins. Results: The results of pathological staining showed that intimal hyperplasia was severe after diabetes-induced lower limb ischemia in rabbits at 4 weeks, and liraglutide treatment reduced symptoms. Liraglutide treatment significantly decreased MDA content, increased SOD, GSH-Px content, and augmented total antioxidant capacity levels in tissues. The results of Western blotting analysis showed that E-cadherin, mitochondrial membrane potential 9 (MMP-9), proliferating cell nuclear antigen (PCNA), and type I collagen protein expression levels were significantly decreased after liraglutide treatment compared with the DM injury group. The results indicated that liraglutide inhibited epithelial-mesenchymal transition (EMT) progression, vascular cell proliferation and migration and collagen production. Liraglutide inhibits transforming growth factor beta 1 (TGF-ß1)/Smad3 signaling pathway protein expression. In vitro assays have shown that liraglutide reduces cellular ROS levels, inhibits cell proliferation and migration and promotes apoptosis. Liraglutide down-regulated the expression of E-cadherin, MMP-9, PCNA, type I collagen protein as well as the TGF-ß1/Smad3 signaling pathway, but this effect could be reversed by tumor necrosis factor alpha (TNF-α). Conclusion: Liraglutide can significantly improve tissue antioxidant capacity, reduce vascular cell proliferation and migration via the TGF-ß1/Smad3 signaling pathway, inhibit the EMT and collagen production processes, and alleviate hyperglycemia(HG)-induced lower limb ischemia and intimal hyperplasia.

Screening of the Active Compounds against Neural Oxidative Damage from Ginseng Phloem Using UPLC-Q-Exactive-MS/MS Coupled with the Content-Effect Weighted Method.

The neuroprotective properties of ginsenosides have been found to reverse the neurological damage caused by oxidation in many neurodegenerative diseases. However, the distribution of ginsenosides in different tissues of the main root, which was regarded as the primary medicinal portion in clinical practice was different, the specific parts and specific components against neural oxidative damage were not clear. The present study aims to screen and determine the potential compounds in different parts of the main root in ginseng. Comparison of the protective effects in the main root, phloem and xylem of ginseng on hydrogen peroxide-induced cell death of SH-SY5Y neurons was investigated. UPLC-Q-Exactive-MS/MS was used to quickly and comprehensively characterize the chemical compositions of the active parts. Network pharmacology combined with a molecular docking approach was employed to virtually screen for disease-related targets and potential active compounds. By comparing the changes before and after Content-Effect weighting, the compounds with stronger anti-nerve oxidative damage activity were screened out more accurately. Finally, the activity of the selected monomer components was verified. The results suggested that the phloem of ginseng was the most effective part. There were 19 effective compounds and 14 core targets, and enriched signaling pathway and biological functions were predicted. After Content-Effect weighting, compounds Ginsenosides F1, Ginsenosides Rf, Ginsenosides Rg1 and Ginsenosides Rd were screened out as potential active compounds against neural oxidative damage. The activity verification study indicated that all four predicted ginsenosides were effective in protecting SH-SY5Y cells from oxidative injury. The four compounds can be further investigated as potential lead compounds for neurodegenerative diseases. This also provides a combined virtual and practical method for the simple and rapid screening of active ingredients in natural products.

[A new approach for optimizing empirical prescriptions of famous physicians based on network target: taking Qingluo Decoction as an example].

Based on the network target approach and technology, this study proposed for the first time a novel optimization method for Chinese medicine formulae. Moreover, with Qingluo Decoction as an example, a method for the research and development of Chinese medicine, which combines scientific methodology and experience of famous doctors, was developed. Specifically, based on the composition of Qingluo Decoction, this study used the using network target for intelligent and quantitative analysis on drug actions(UNIQ) to predict the medicinals that targeted the key pathways of rheumatoid arthritis(RA) such as angiogenesis. Then, combining the experience of the first national Chinese medical master LI Ji-ren and Aihui famous Chinese medicine doctor LI Yan and Chinese medicine theory, this study developed a novel angiogenesis-targeted prescription modified Qingluo Decoction(MQLD). Afterward, the clinical efficacy and mechanism of MQLD were verified. The results showed that 27 medicinals with significant regulatory effect on angiogenesis-related key signaling pathways were identified by UNIQ, among which 6 were selected by the Chinese medicine physicians to develop the MQLD. Clinical trials demonstrated that the clinical efficacy of MQLD, in terms of either American College of Rheumatology 20% improvement and 50% improvement criteria(ACR20, ACR50) or TCM syndrome evaluation, was better than that of Qingluo Decoction. Experimental study revealed that MQLD can inhibit RA angiogenesis by acting on the vascular endothelial growth factor(VEGF) pathway, nuclear factor κB(NF-κB) pathway, inflammatory cytokine release, and immune cell regulation. Taken together, this study developed a new formula MQLD with improved clinical efficacy, precise applicable clinical settings, and authorized patent through the network target technology, thus providing a new way for the precise development of Chinese medicine and preservation of the experience of famous physicians.

The interactive association between sodium intake, alcohol consumption and hypertension among elderly in northern China: a cross-sectional study.

BACKGROUND: Hypertension is a worldwide public health problem. We sought to examine the interactive associations among sodium intake, alcohol consumption and hypertension among older adult residents of Inner Mongolia in northern China. METHODS: This cross-sectional study used data from the National Survey for Nutrition and Adult Chronic Disease in Inner Mongolia. The prevalence of hypertension was age standardized by the direct method. Sodium intake and alcohol consumption were estimated using a weighing method and 24-h recalls on 3 consecutive days. Hypertension was either self-reported or field-measured. Participants were categorized into six subgroups according to combinations of sodium intake status and drinking level. Logistic regression was used to determine the interactive effect of sodium intake and drinking on hypertension. RESULTS: Of the 820 older adults who participated in this study, 523 (63.80%, age-standardized rate = 62.33%) had been diagnosed with hypertension. The mean sodium intake was 4.88 g. Sodium intake and drinking excessively were both independently related to higher risk of hypertension. A formal test for a multiplicative interaction between sodium intake and drinking revealed a significant interaction (p = 0.042), and the multivariable-adjusted odds ratio (95% CI) for the interaction was 1.1 (1.0-1.3). After adjusting for confounders, compared with moderate sodium intake and no drinking group, the risk of hypertension was highest among those with both excessive sodium intake and excessive alcohol consumption, with an odds ratio of 3.6 (95% CI: 1.7-7.9). CONCLUSIONS: The study highlights the interactive effect of sodium intake and alcohol consumption on hypertension. Primary health care providers should pay special attention to older adults with hypertension-especially those with an unhealthy diet including both excessive sodium and excessive alcohol intake. These findings are applicable for older adults in Inner Mongolia and worldwide.

Pooled analysis of LAMP assay for the diagnosis of norovirus infection.

BACKGROUND: Rapid laboratory detection is essential to diagnose norovirus infection. LAMP has many advantages compared with RT-PCR for detecting norovirus, including high sensitivity, high specificity, rapidity, low cost, and intuitive results, which can be easily read with the naked eye with the help of color-based reporters. In this study, we intend to analyze the accuracy of LAMP methods for the diagnosis of norovirus infection. METHODS: Two researchers independently retrieved relevant literature up to January 2021 (PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, and VIP). The researchers screened all articles and extracted their research data for meta-analysis. QUADAS-2 tool was used to evaluate the quality of the included studies by Review Manager 5.3. Forest plots were performed by Meta-DiSc 1.4 to evaluate the accuracy of the test. Deeks' funnel plot symmetry tests were conducted by Stata 15.0 to check the potential publication bias. RESULTS: Eleven sets of data extracted from the eight included studies were included for meta-analysis. For the detection of norovirus, the pooled sensitivity, specificity, positive LR, negative LR, diagnostic OR, and their 95% CI were 0.96 (0.95-0.97), 0.99 (0.99-1.00), 91.14 (31.88-260.56), 0.06 (0.04-0.09), and 1473.68 (562.96-3857.70), respectively. Besides, AUC in the SROC curve was 0.9920. CONCLUSION: LAMP had high sensitivity and specificity in terms of the diagnosis of norovirus infection. However, further extension of this approach should be researched to ensure the accuracy and practicability of this hopeful test in the future.

Diet quality is associated with reduced risk of hypertension among Inner Mongolia adults in northern China.

OBJECTIVE: The present study investigated the association between dietary patterns and hypertension applying the Chinese Dietary Balance Index-07 (DBI-07). DESIGN: A cross-sectional study on adult nutrition and chronic disease in Inner Mongolia. Dietary data were collected using 24 h recall over three consecutive days and weighing method. Dietary patterns were identified using principal components analysis. Generalized linear models and multivariate logistic regression models were used to examine the associations between DBI-07 and dietary patterns, and between dietary patterns and hypertension. SETTING: Inner Mongolia (n 1861). PARTICIPANTS: A representative sample of adults aged ≥18 years in Inner Mongolia. RESULTS: Four major dietary patterns were identified: 'high protein', 'traditional northern', 'modern' and 'condiments'. Generalized linear models showed higher factor scores in the 'high protein' pattern were associated with lower DBI-07 (ßLBS = -1·993, ßHBS = -0·206, ßDQD = -2·199; all P < 0·001); the opposite in the 'condiments' pattern (ßLBS = 0·967, ßHBS = 0·751, ßDQD = 1·718; all P < 0·001). OR for hypertension in the highest quartile of the 'high protein' pattern compared with the lowest was 0·374 (95 % CI 0·244, 0·573; Ptrend < 0·001) in males. OR for hypertension in the 'condiments' pattern was 1·663 (95 % CI 1·113, 2·483; Ptrend < 0·001) in males, 1·788 (95 % CI 1·155, 2·766; Ptrend < 0·001) in females. CONCLUSIONS: Our findings suggested a higher-quality dietary pattern evaluated by DBI-07 was related to decreased risk for hypertension, whereas a lower-quality dietary pattern was related to increased risk for hypertension in Inner Mongolia.

Optimized design of the light source for an indoor visible light communication system based on an improved bat algorithm.

Aiming at the problem of uneven distribution of receiving illuminance and optical power on the receiving plane of the visible light communication (VLC) system, this paper proposes a light source optimization method based on an improved bat algorithm (IBA). Taking the rectangular and hybrid layouts with 16 light-emitting diodes (LEDs), as examples, we set the variance of received light power on the receiving plane as the fitness function. By redesigning the speed update method and local search method of the traditional bat algorithm (BA), the IBA is used to optimize the LED half-power angle and LED position that affect the system performance. The simulation results show that, considering the primary reflection of the wall, the method can reduce the received illumination and optical power fluctuation of the receiving plane within a limited number of iterations under different light source layout schemes.

Potential of constructed wetland treatment systems for agricultural wastewater reuse under the EU framework.

One of the solutions for the problems regarding increasing water scarcity and pollution of water resources can be wastewater reuse. Constructed wetlands (CWs) are a sustainable and cost-effective technology for wastewater treatment. If they are able to produce effluent of a needed quality, they can be a valuable addition for wastewater reuse schemes. This review studied 39 treatment systems based on CWs, and it assessed their characteristics and performance on pollutant removal. Moreover, their potential to reach the new European Union standards for agricultural wastewater reuse was evaluated. The results showed that the combination of CWs with additional technologies (e.g. UV treatment, anaerobic reactors) can further increase their performance and provide better removal efficiencies in comparison with conventional horizontal and vertical subsurface flow CWs. Particularly, hybrid systems showed a better removal of organic matter and bacterial indicators than single-stage CWs. For most of the systems considered, the concentrations of biochemical oxygen demand and total suspended solids in treated effluent were below the limits for agricultural reuse. However, that was often not the case with Escherichia coli and therefore it is recommended to add a disinfection unit to the systems in order to achieve the levels required in the case of agricultural reuse.

Downregulation of microRNA-143-5p is required for the promotion of odontoblasts differentiation of human dental pulp stem cells through the activation of the mitogen-activated protein kinases 14-dependent p38 mitogen-activated protein kinases signaling pathway.

MicroRNAs (miRNAs) play critical roles in various biological processes including cell differentiation. Some researchers suggested that the p38 mitogen-activated protein kinases (MAPK) signaling pathway had an effect on regulating the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). This study focuses on the effects of miR-143-5p on hDPSCs by regulating the p38 MAPK signaling pathway. The targeting relationship of MAPK14 and miR-143-5p targets were verified by TargetScan and dual-luciferase reporter gene assay. Through overexpression of miR-143-5p or silencing of miR-143-5p, expressions of miR-143-5p, MAPK14, Ras, MAPK kinase (MKK) 3/6, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), and osteocalcin (OCN) were detected by reverse transcription quantitative polymerase chain reaction. Protein expressions of MAPK14, Ras, and MKK3/6 were determined by western blot analysis. ALP and alizarin red S staining were used to detect mineralization. Initially, MAPK14 was found to be negatively regulated by miR-143-5p. Meanwhile, the upregulated miR-143-5p decreased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. On the contrary, the downregulated miR-143-5p increased the p38 MAPK signaling pathway related genes (MAPK14, Ras, and MKK3/6) and odontoblastic differentiation markers (ALP, DSPP, and OCN) expression. Furthermore, ALP activity and mineralized nodules increased after downregulation of miR-143-5p, and after its upregulation, ALP activity and mineralized nodules decreased. Our data suggest that poor expression of miR-143-5p promotes hDPSCs odontoblastic differentiation through the activation of the p38 MAPK signaling pathway by upregulating MAPK14.

Indoor three-dimensional high-precision positioning system with bat algorithm based on visible light communication.

A three-dimensional (3-D) positioning system on the basis of bat algorithm (BA) using visible light communication is proposed in this work. BA is a global optimization algorithm that can be used to solve the indoor positioning problem. In BA, the positioning process is considered to be a process of searching for the receiver by many bats in an indoor space of 3 m×3 m×4 m. Therefore, taking advantage of the bat search algorithm, 3-D low-complexity and high-precision indoor positioning is able to be actualized when the number of iterations reaches a certain condition. The simulation results show that the system can achieve high-precision positioning at different signal-to-noise ratios. Meanwhile, a trajectory tracking experiment is carried out to validate the good performance of this positioning system. The proposed algorithm is a positioning method with good potential in various positioning applications.

Pharmacokinetics of sanguinarine, chelerythrine, and their metabolites in broiler chickens following oral and intravenous administration.

Sanguinarine (SA) and chelerythrine (CHE) are the main active components of the phytogenic livestock feed additive, Sangrovit®. However, little information is available on the pharmacokinetics of Sangrovit® in poultry. The goal of this work was to study the pharmacokinetics of SA, CHE, and their metabolites, dihydrosanguinarine (DHSA) and dihydrochelerythrine (DHCHE), in 10 healthy female broiler chickens following oral (p.o.) administration of Sangrovit® and intravenous (i.v.) administration of a mixture of SA and CHE. The plasma samples were processed using two different simple protein precipitation methods because the parent drugs and metabolites are stable under different pH conditions. The absorption and metabolism of SA following p.o. administration were fast, with half-life (t1/2 ) values of 1.05 ± 0.18 hr and 0.83 ± 0.10 hr for SA and DHSA, respectively. The maximum concentration (Cmax ) of DHSA (2.49 ± 1.4 µg/L) was higher that of SA (1.89 ± 0.8 µg/L). The area under the concentration vs. time curve (AUC) values for SA and DHSA were 9.92 ± 5.4 and 6.08 ± 3.49 ng/ml hr, respectively. Following i.v. administration, the clearance (CL) of SA was 6.79 ± 0.63 (L·h-1 ·kg-1 ) with a t1/2 of 0.34 ± 0.13 hr. The AUC values for DHSA and DHCHE were 7.48 ± 1.05 and 0.52 ± 0.09 (ng/ml hr), respectively. These data suggested that Sangrovit® had low absorption and bioavailability in broiler chickens. The work reported here provides useful information on the pharmacokinetic behavior of Sangrovit® after p.o. and i.v. administration in broiler chickens, which is important for the evaluation of its use in poultry.

Screening of the Active Component Promoting Leydig Cell Proliferation from Lepidium meyenii Using HPLC-ESI-MS/MS Coupled with Multivariate Statistical Analysis.

Lepidium meyenii is now widely consumed as a functional food and medicinal product, which is known as an enhancer of reproductive health. However, the specific chemical composition and mechanism of action for improving sexual function are unclear. The present study aims at screening and determining the potential compounds, which promote mouse leydig cells (TM3) proliferation. The partial least squares analysis (PLS) was employed to reveal the correlation between common peaks of high performance liquid chromatography (HPLC) fingerprint of L. meyenii and the proliferation activity of TM3. The results suggested that three compounds had good activities on the proliferation of TM3 and promoting testosterone secretion, there were N-benzyl-hexadecanamide, N-benzyl-(9z,12z)-octadecadienamide and N-benzyl-(9z,12z,15z)-octadecatrienamide which might be the potential bioactive markers related to the enhancing sexual ability functions of L. meyenii. The first step in testosterone synthesis is the transport of cholesterol into the mitochondria, and the homeostasis of mitochondrial function is related to cyclophilin D (CypD). In order to expound how bioactive ingredients lead to promoting testosterone secretion, a molecular docking simulation was used for further illustration in the active sites and binding degree of the ligands on CypD. The results indicated there was a positive correlation between the binding energy absolute value and testosterone secretion activity. In addition, in this study it also provided the reference for a simple, quick method to screen the promoting leydig cell proliferation active components in traditional Chinese medicine (TCM).

Effect of Nanotube Morphologies on Multi-Walled Carbon Nanotubes Based Counter Electrode for Dye-Sensitized Solar Cell.

Multi-walled carbon nanotubes (MWCNTs) with different morphologies were introduced into dyesensitized solar cell (DSSC) as low-cost substitutes for Pt counter electrode (CE). The effect of length and orientation of MWCNTs on the power conversion efficiency (PCE) of DSSC with MWCNTs CE were studied by measuring electrochemical impedance spectroscopy of MWCNTs and the photocurrent density­voltage (J­V ) characteristics of DSSC in this study. Results revealed that the long MWCNTs showed better electrocatalytic activity of reducing triiodide ions than short MWCNTs and yielded the power conversion efficiency of 2.42%. When the aligned multi-walled carbon nanotubes (AMWCNTs) with the same length as the long MWCNTs were used to prepare the CE, the power conversion efficiency of the DSSC reaches 2.95%. In order to further improve the performance of the DSSC, the processing of photoanode and counter electrode were adjusted. The power conversion efficiency of the cell with AMWCNTs as CE prepared by adjusted processing achieved 3.95% and the short circuit current density is superior to the DSSC with Pt as CEs, and it indicated the adjusted processing is beneficial to increase the overall performance of the dye-sensitized solar cell.

Novel magnetic properties of CoTe nanorods and diversified CoTe2 nanostructures obtained at different NaOH concentrations.

CoTe and CoTe2 nanorods with average diameter of 100 nm were synthesized by a simple hydrothermal process, and different CoTe2 nanostructures were obtained by changing the NaOH concentration. CoTe nanorods exhibit weak ferromagnetism while CoTe2 nanorods present paramagnetic behavior. Different magnetic behaviors occur in the other CoTe2 nanostructures due to Na+ entrance into CoTe2 crystals. A first-principles study on Na-doped CoTe2 confirms the magnetic characteristics.

[Treatment of triple negative breast cancer cells with combination of mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901].

MEK inhibition activates PI3K/AKT/mTOR pathway in triple negative breast cancer (TNBC) cell lines. Combination of PI3K inhibitor and MEK1/2 inhibitor is not appropriate for PI3K inhibitor insensitive TNBC cell lines. This study was designed to investigate the effects of dual treatments with mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901 in MDA-MB-435 cell line. MEK1/2 inhibition led to activation of AKT, which is the downstream signaling protein of PI3K pathway. The combination inhibited the phosphorylation of AKT and therefore abolished the feedback interaction of two pathways. Cell proliferation assay and DNA replication assay demonstrated that the dual treatments led to a significant synergistic inhibition of cell cycle progression and cell proliferation.