Molecular characterization of the grass carp bscl2 gene and its expression response to lipid accumulation, nutritional status, insulin and glucagon.

Bscl2 plays a role in lipid metabolism of mammals, however its role in teleost fish remains unclear. Using the grass carp (Ctenopharyngodon idella) as a model, the bscl2 gene was isolated from the brain and characterized. Thereafter, the tissue distribution of the gene was examined, before expression was analyzed as a function of fasting, refeeding, oral glucose administration and overfeeding. In addition, bscl2 mRNA levels were evaluated in grass carp primary hepatocytes treated with glucagon, insulin, oleic acid, and glucose. Results showed that the cloned bscl2 gene was 1341 bp, encoding 446 amino acids, and was highly expressed in the brain, heart, and gonad. Following oral glucose administration, bscl2 expression increased. Expression of bscl2 decreased in fasted fish but increased following refeeding. Overfeeding, which resulted in elevated lipid accumulation, also stimulated bscl2 expression. In primary hepatocytes, bscl2 levels were increased by glucose, oleic acid, and insulin treatments, and reduced by glucagon treatment. These data suggest that bscl2 may play an important role in nutrient metabolism in teleost fish.

Cloning grass carp (Ctenopharyngodon idella) ccdc3 and its expression affected by nutrition state, insulin, and glucagon.

As an adipokine, coiled-coil domain-containing 3 (CCDC3) plays multiple physiological roles in fatty liver, lipid metabolism, and abdominal obesity. Grass carp was selected as the experimental animal in this study to investigate the roles of Ccdc3 in teleosts. Results showed that the open reading frame (ORF) of cloned ccdc3 was 831 bp and encoded 276 amino acids. Three N-glycosylation sites and a predicted coiled-coil domain motif were located in the identified Ccdc3. Moreover, a nuclear localization signal (NLS) was contained in the coiled-coil domain motif of the identified Ccdc3. The results on tissue distribution revealed that ccdc3 was highly detected in grass carp fat and brain tissue. In the oral glucose tolerance test (OGTT), the expression of ccdc3 increased remarkably in the brain, hypothalamus, and visceral fat in the glucose treatment group. In the fasting and refeeding experiment, the ccdc3 expression levels were remarkably reduced in the brain, hypothalamus, and visceral fat after 14 days of fasting. In the refeeding group, the ccdc3 expression levels were considerably elevated compared with those in the fasting group. In the induced overfeeding experiment, the ccdc3 expression increased remarkably in the hepatopancreas, brain, and visceral fat tissues. The ccdc3 expression in the primary hepatocytes was remarkably increased with glucose, oleic acid, and insulin treatment. However, ccdc3 expression was markedly decreased with glucagon treatment. In conclusion, these results indicate that Ccdc3 is involved in regulating glucose and lipid metabolism of teleosts.

Relationship between air pollutants and spontaneous abortion in a coal resource valley city: a retrospective cohort study.

OBJECTIVE: Pollutants in the atmosphere have been linked to poor pregnancy outcomes in women. However, such investigations are scarce in metropolitan northern China. The major exposure window of air pollution affecting pregnant women is also unknown. METHODS: For the analysis, this retrospective cohort study enrolled 6960 pregnant women recorded at Tongchuan People's Hospital from January 2018 to December 2019. Pollutant concentration values from the nearest monitoring station to the pregnant women were used to estimate exposure doses for each exposure window. Logistic regression models were created to investigate the connection between pollutants and spontaneous abortion while controlling for confounding factors. RESULTS: PM2.5 was a risk factor for spontaneous abortion in T3 (30-60 days before the first day of the last menstrual period [LMP]), (OR: 1.305, 95% CI: 1.143-1.490) and T4 (60-90 days before the first day of the LMP),(OR: 1.450, 95% CI: 1.239-1.696) after controlling for covariates. In the same window, PM10 was a risk factor (OR: 1.308, 95% CI: 1.140-1.500), (OR: 1.386, 95% CI: 1.184-1.621). In T2 (30 days before the first day of the LMP), T3, and T4, SO2 was a risk factor for spontaneous abortion (OR: 1.185, 95% CI: 1.025-1.371), (OR: 1.219, 95% CI: 1.071-1.396), (OR: 1.202, 95% CI: 1.040-1.389). In T3 and T4, NO2 was a risk factor (OR: 1.171, 95% CI: 1.019- 1.346), (OR: 1.443, 95% CI: 1.259-1.655). In T1 (from the first day of the LMP to the date of abortion), O3 was found to be a risk factor (OR: 1.366, 95% CI: 1.226-1.521). CONCLUSION: Exposure to high levels of air pollutants before and during pregnancy may be a risk factor for spontaneous abortion in pregnant women. This study further illustrates the importance of reducing air pollution emissions.

Polarizable atomic multipole-based force field for cholesterol.

Cholesterol is one of the essential component of lipid in membrane. We present a polarizable atomic multipole force field (FF) for the molecular dynamic simulation of cholesterol. The FF building process follows the computational framework as the atomic multipole optimized energetics for biomolecular applications (AMOEBA) model. In this framework, the electronics parameters, including atomic monopole moments, dipole moments, and quadrupole moments calculated from ab initio calculations in the gas phase, are applied to represent the charge distribution. Furthermore, the many-body polarization is modeled by following the same pattern of distributed atomic polarizabilities. Then, the bilayers composed of two typical phospholipid molecules, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), in a range of different cholesterol concentrations are built and implemented by molecular dynamics (MD) simulations based on the proposed polarizable FF. The simulation results are statistically analyzed to validate the feasibility of the proposed FF. The structural properties of the bilayers are calculated to compare with the related experimental values. The MD values show the same trend of experimental values changes.Communicated by Ramaswamy H. Sarma.

The effectiveness of an online sexuality education module in promoting sexual knowledge and attitude change: a cluster randomized controlled trial.

This study assesses the ability of an online sexuality education (OSE) module ('You and Me') to enhance sexual and reproductive health (SRH) knowledge and attitudes among 10th-grade vocational high school students in China. We conducted a cluster randomized controlled trial, randomizing 29 vocational high schools to (i) receiving the module (intervention) or (ii) not receiving the module (control). Students completed a baseline questionnaire, then completed the module within 8 weeks and then completed a follow-up questionnaire within the following 2 weeks. We assessed the differences in intervention effects using hierarchical linear modeling. No significant differences between intervention and control groups were found for knowledge and attitude scores at baseline among the 2985 students included in the analyses. For the intervention group at follow-up, we observed significant improvements in SRH knowledge scores of approximately 20% for boys and girls although girls responded to the module with larger knowledge gains than boys. At follow-up, intervention group students also had higher SRH attitude scores toward views that are more contemporary than the control group. In addition, girls held more contemporary attitudes than boys. The comprehensive OSE module assessed is effective in improving SRH knowledge, and attitude among Chinese vocational high school students after the module is completed.

Modeling the progression of Type 2 diabetes with underlying obesity.

Environmentally induced or epigenetic-related beta-cell dysfunction and insulin resistance play a critical role in the progression to diabetes. We developed a mathematical modeling framework capable of studying the progression to diabetes incorporating various diabetogenic factors. Considering the heightened risk of beta-cell defects induced by obesity, we focused on the obesity-diabetes model to further investigate the influence of obesity on beta-cell function and glucose regulation. The model characterizes individualized glucose and insulin dynamics over the span of a lifetime. We then fit the model to the longitudinal data of the Pima Indian population, which captures both the fluctuations and long-term trends of glucose levels. As predicted, controlling or eradicating the obesity-related factor can alleviate, postpone, or even reverse diabetes. Furthermore, our results reveal that distinct abnormalities of beta-cell function and levels of insulin resistance among individuals contribute to different risks of diabetes. This study may encourage precise interventions to prevent diabetes and facilitate individualized patient treatment.

The progression of secondary diabetes: A review of modeling studies.

Mathematical modeling has provided quantitative information consistent with experimental data, greatly improving our understanding of the progression of type 1 and type 2 diabetes. However, diabetes is a complex metabolic disease and has been found to be involved in crosstalk interactions with diverse endocrine diseases. Mathematical models have also been developed to investigate the quantitative impact of various hormonal disorders on glucose imbalance, advancing the precision treatment for secondary diabetes. Here we review the models established for the study of dysglycemia induced by hormonal disorders, such as excessive glucocorticoids, epinephrine, and growth hormone. To investigate the influence of hyperthyroidism on the glucose regulatory system, we also propose a hyperthyroid-diabetes progression model. Model simulations indicate that timely thyroid treatment can halt the progression of hyperglycemia and prevent beta-cell failure. This highlights the diagnosis of hormonal disorders, together withblood sugar tests, as significant measures for the early diagnosis and treatment of diabetes. The work recapitulates updated biological research on the interactions between the glucose regulatory system and other endocrine axes. Further mathematical modeling of secondary diabetes is desired to promote the quantitative study of the disease and the development of individualized diabetic therapies.

A unified mathematical model of thyroid hormone regulation and implication for personalized treatment of thyroid disorders.

Current clinician practice for thyroid hormone regulation of patients is based upon guesswork and experience rather than quantified analysis, which exposes patients under longer risk and discomfort. To quantitatively analyze the thyroid regulation for patients of different thyroid states, we develop a two-dimensional mathematical model that can be applied to analyze the dynamic behaviors of thyroid hormones with or without drug intervention. The unified model can be employed to study the regulation of TSH (thyroid-stimulating hormone) and FT4 (free thyroxine) for euthyroid (normal thyroid) subjects, Hashimoto's thyroiditis, and Graves' disease patients, respectively. The results suggest that the level of TPOAb (thyroid peroxidase antibody) may be a factor determining whether the patient would progress from euthyroid state to subclinical or clinical hypothyroidism, and that increased TRAb (TSH receptor antibody) may lead Graves' disease to deteriorate from the early stage to overt hyperthyroidism. Given the early blood-test data, we demonstrate the feasibility for healthcare professionals to apply our model in choosing an appropriate dosage regimen for patients to achieve the desired TSH and FT4 levels within a specified time frame. This proposed model has the potential to optimize personalized treatment and shorten the therapeutic time for patients suffering from Hashimoto's thyroiditis and Graves' disease.

[Betaine induces apoptosis of C4-2B prostate cancer cells via inhibiting PI3K/AKT/NF-κB signaling pathway].

Objective To investigate the inhibitory effect of betaine (BET) on the proliferation of C4-2B prostate cancer cells and its possible mechanism. Methods C4-2B cells were treated with 0, 100, 200, 400, 600, 800 mmol/L BET. CCK-8 assay was used to assess the cell proliferation, plate cloning formation assay to detect clone formation ability and flow cytometry to evaluate cell apoptosis, and the cell morphological alteration was observed by microscopy. The protein expression of BAX, Bcl2, cleaved caspase 3 (c-caspase-3), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and NF-κB p65 were detected by Western blotting, and the changes of BAX, Bcl2, c-caspase-3, and NF-κB p65 proteins were further verified after the cells were treated with NF-κB pathway inhibitor BAY11-7082. Results BET inhibited the proliferation of C4-2B cells in a dose-dependent manner. The 50% inhibitory concentration (IC50) was 422.7 mmol/L after the cells were treated with BET for 48 hours. Compared with the control group (0 mmol/L BET treatment), the proliferation of C4-2B cells was inhibited along with morphological changes, decreased clone formation ability and increased apoptosis rate in 200, 300, 400 mmol/L BET treated groups. Meanwhile, the protein expression of BAX and c-caspase-3 were up-regulated and Bcl2, PI3K, AKT and NF-κB p65 were down-regulated in 300, 400 mmol/L BET groups as compared with the control group. After BAY11-7082 treatment alone, Bcl2, BAX, c-caspase-3, NF-κB p65 protein expression trend was consistent with that of the 300 mmol/L BET treated group, and Bcl2, NF-κB p65 protein expression levels were lower and BAX and c-caspase-3 protein expression levels were higher in BET combined with BAY11-7082 treated group. Conclusion BET can inhibit C4-2B cell proliferation and induce its apoptosis by blocking PI3K/AKT/NF-κB signaling pathway.

Edwardsiella tarda induces enteritis in farmed seahorses (Hippocampus erectus): An experimental model and its evaluation.

Bacterial enteritis is an important deadly threat to farmed seahorses. However, its pathogenesis is obscure because of the paucity of reproducible experimental intestinal inflammation models. Herein, a strain of Edwardsiella tarda YT1 from farmed seahorse Hippocampus erectus was isolated and identified by morphological, phylogenetic, and biochemical analysis, and confirmed as a pathogen of enteritis for the first time by challenge experiment. Two E. tarda concentrations (1 × 105 and 1 × 107 colony forming units [cfu] ml-1) were confirmed suitable for an enteritis model by intraperitoneal injection. To develop and evaluate the experimental model, we challenged seahorses with E. tarda and found that (1) the infection inhibited body length increase, significantly decreased body weight (P < 0.05), and induced typical pathological features including anorexia, anal inflammation, and intestinal fluid retention; (2) 19 external (weight, height, anal inflammation, feeding status, and intestinal fluid retention), histological (goblet and inflammatory cell numbers and thickening of lamina propria and muscularis mucosae), and molecular (hepcidin, liver-expressed antimicrobial peptide, lysozyme, piscidin, interleukin [IL]-1ß, IL-1ß receptor, IL-2, IL-10, interferon1, tumor necrosis factor [TNF]-α, and toll-like receptor 5 [TLR5]) indicators were suitable for model evaluation, as they could sensitively respond and varied similarly throughout the experiment, indicating the high sensitivity of seahorses against pathogen invasion; (3) TLR5 may play an essential role in triggering host immune responses during E. tarda-induced chronic enteritis, and (4) the evaluating system could reflect the pattern and intensity of disease progression. Thus, we developed an experimental model and an evaluating system of bacterial enteritis in farmed seahorses, helping us to reveal the pathogenesis of bacterial enteritis, identify potential therapeutic drugs, and search suitable genetic markers for seahorse molecular breeding.