IntroductionThe objective of the study was to identify trends in incidence of adult diffuse gliomas in the United States and evaluate the contribution of age, period, and cohort effects to the trends.MethodsUsing the Surveillance, Epidemiology, and End Results 9 database, primary diffuse glioma patients (≥20 years old) diagnosed from 1973 to 2014 were identified. Incidence trends were analyzed using joinpoint regression and age‐period‐cohort modeling.ResultsOverall, the incidence for adult glioma decreased slowly from 1985 to 2014 (annual percent change [APC] = 0.5%, 95% confidence intervals [CI], 0.3%‐0.6%). In histology subtype‐stratified analysis, glioblastoma and nonglioblastoma exhibited opposite trends. The incidence for glioblastoma increased from 1978 to 2014 (APC for year 1978‐1992 = 2.7%, 95% CI, 1.8%‐3.6%; APC for 1992‐2014 = 0.3%, 95% CI, 0%‐0.6%), while the incidence for nonglioblastoma decreased significantly from 1982 to 2014 (APC = 2.2%, 95% CI, 2.0%‐2.5%). Age‐period‐cohort modeling revealed significant period and cohort effects, with the patterns for glioblastoma and nonglioblastoma distinctive from each other. Compared with adults born 1890s, those born 1920s had approximately 4‐fold the risk of glioblastoma after adjustment of age and period effects, while the risk of nonglioblastoma was reduced by half in individuals in the 1939 cohort as compared with those in the 1909 cohort.ConclusionsThe results support the hypothesis of etiological heterogeneity of diffuse gliomas by histology subtypes. The established risk factors cannot fully explain the distinct patterns by histology subtypes, which necessitate further epidemiological studies.

BackgroundDuring peripartum period, dairy cows are highly susceptible to energy metabolism disorders such as fatty liver and ketosis. Angiopoietin-like protein 4 (ANGPTL4) and fibroblast growth factor 21 (FGF21), known as hepatokines, play important roles in lipid metabolism. The purposes of our study were to evaluate variations of serum ANGPTL4 and FGF21 concentrations in periparturient dairy cows and changes in these serum analyte concentrations of energy-related metabolic disorders in early lactation dairy cows.This study was divided into two experiments. Experiment I: Blood parameters were measured in healthy periparturient Holstein cows from 4 wk antepartum to 4 wk postpartum (n = 219). In this experiment, weekly blood samples were obtained from 4 wk before the expected calving date through 4 wk after calving. Experiment II: Blood parameters were measured in healthy cows (n = 30) and cows with clinical ketosis (n = 29) and fatty liver (n = 25) within the first 4 wk of lactation. In the present study, all blood samples were collected from the coccygeal vein in the early morning before feeding.ResultsSerum ANGPTL4 and FGF21 concentrations peaked at parturition, and declined rapidly over the following 2 wk Serum ANGPTL4 and FGF21 concentrations were positively correlated with serum non-esterified fatty acids (NEFA) concentration (r = 0.856, P = 003; r = 0.848, P = 0.004, respectively). Cows with clinical ketosis and fatty liver had significantly higher serum ANGPTL4 and FGF21 concentrations than healthy cows (P < 0.01).ConclusionSerum ANGPTL4 and FGF21 concentrations were elevated during peripartum period, suggesting that energy balance changes that were associated with parturition contributed significantly to these effects. Although FGF21 and ANGPTL4 could play important roles in the adaptation of energy metabolism, they may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period.

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

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Swainsonine (SW), an indolizidine alkaloid extracted from locoweeds, was shown toxic effects in multiple studies, but the underlying action mechanism remains unclear. SW is known to cause autophagy and apoptosis, but there has been no report on paraptosis mediated cell death. Here, we showed that SW induced rat primary renal tubular epithelial cells (RTECs) death accompanied by vacuolation in vitro. The fluorescence with the endoplasmic reticulum (ER)-Tracker Red and transmission electron microscopy (TEM) results indicated that the vacuoles were of ER origin, typical of paraptosis. The level of ER stress markers, such as polyubiquitinated proteins, Bip, CHOP and cytoplasmic concentration of Ca2+ have drastically increased. Interestingly, autophagy inhibitor could not interrupt but enhanced the induction of cytoplasmic vacuolization. Furthermore, MAPK pathways were activated by SW and inhibitors of ERK and JNK pathways could prevent the formation of cytoplasmic vacuolization. In this study, we confirmed that SW induced cell paraptosis through ER stress and MAPK signaling pathway, thus further laying a theoretical foundation for the study of SW toxicity mechanism.

SummaryNegative energy balance is considered as the pathological basis of energy metabolic disorders in periparturient dairy cows. Serum non-esterified fatty acids (NEFA) are one higher than that of the control group (p < .05). The FGF21 expression and secretion were similar at 1.2, 1.8 and 2.4 mmol/L NEFA-treated hepatocytes and significantly higher than those observed for controls (p < .01). These data suggest that high concentrations of NEFA significantly promote FGF21 expression and secretion in bovine hepatocytes. In particular, this promotion occurs in a dose-dependent manner and may be involved in the pathological processes of energy metabolism disorders of dairy cows in the peripartum period. K E Y W O R D Sdairy cow, hepatocyte, hepatokine, negative energy balance, peripartum period

The transforming growth factors β1 (TGF-β1) and TGF-β2, as two distinct homodimers of TGF-β superfamily, involve in chondrocyte growth and differentiation. Emerging evidence has implied that strontium (Sr) plays an important role in the bone formation and resorption, and has strong effects on stimulating human cartilage matrix formation in vitro. However, the direct effects of Sr on TGF-β1 and TGF-β2 expressions in chondrocytes are not entirely clear. The purpose of this study was to evaluate the influence of different Sr concentrations on the expression of TGF-β1 and TGF-β2 in rat chondrocytes in vitro. Chondrocytes were isolated from Wistar rat articular by enzymatic digestion. Strontium chloride hexahydrate (SrCl·6HO) was used as a Sr source in this study. Sr was added to the culture solution at final concentrations of 0, 0.5, 1.0, 2.0, 5.0, 20.0, and 100 μg/mL. After 72 h of continuous culture, TGF-β1 and TGF-β2 mRNA abundance and protein expression levels in the chondrocytes were determined by real-time polymerase chain reaction (real-time PCR) and Western blot, respectively. The results showed that TGF-β1 and TGF-β2 expressions in chondrocytes increased dose-dependently with Sr concentration. The mRNA abundance of TGF-β1 and TGF-β2 were markedly higher than those observed for control (P < 0.01) when the Sr-treated concentration exceeded 1.0 and 5.0 μg/mL, respectively. The TGF-β1 and TGF-β2 protein expression levels were extremely significantly higher than those in the control group (P < 0.01) at above 5.0 μg/mL Sr-treatment. These results indicated that Sr could involve in the chondrocytes metabolism via regulating TGF-β1 and TGF-β2 signalling.