F6P/G6P-mediated ChREBP activation promotes the insulin resistance-driven hepatic lipid deposition in zebrafish.

Insulin-sensitive lipogenesis dominates the body lipid deposition; however, nonalcoholic fatty liver disease (NAFLD) develops in the insulin-resistant state. The regulation mechanism of insulin resistance-driven NAFLD remains elusive. Using zebrafish model of insulin resistance (ZIR, insrb-/-) and mouse hepatocytes (NCTC 1469), we explored the regulation mechanism of insulin resistance-driven hepatic lipid deposition under the stimulation of carbohydrate diet (CHD). In ZIR model, insulin resistance induced hyperlipidemia and elevated hepatic lipid deposition via elevating the gene/protein expressions of lipogenic enzymes, that was activated by carbohydrate response element binding protein (ChREBP), rather than sterol regulatory element binding proteins 1c (SREBP-1c). The metabolomic analysis in zebrafish and silencing of chrebp in mouse hepatocytes revealed that the increased hepatic frucotose-6-phosphate (F6P) and glucose-6-phosphate (G6P) promoted the ChREBP-mediated lipid deposition. We further identified that F6P alone was sufficient to activate ChREBP-mediated lipid deposition by a SREBP-1c-independent manner. Moreover, we clarified the suppressed hepatic phosphofructokinase/glucose-6-phosphatase functions and the normal glucokinase function preserved by glucose transporter 2 (GLUT2) manipulated the increased F6P/G6P content in ZIR. In conclusion, the present study revealed that insulin resistance promoted hepatic lipid deposition via the F6P/G6P-mediated ChREBP activation. Our findings deciphered the main regulation pathway for the liver lipid deposition in the insulin-resistant state and identified F6P as a new potential regulator for ChREBP.

Effects of fish meal replacement with Chlorella meal on growth performance, pigmentation, and liver health of largemouth bass (Micropterus salmoides).

Chlorella meal is a potential protein source for aquafeeds. However, the physiological response of carnivorous fish fed Chlorella meal remains elusive. This study evaluated the effects of replacing dietary fish meal with Chlorella meal on growth performance, pigmentation, and liver health in largemouth bass. Five diets were formulated to replace dietary fish meal of 0% (C0, control), 25% (C25), 50% (C50), 75% (C75), and 100% (C100) with Chlorella meal, respectively. Total 300 fish (17.6 ± 0.03 g) were randomly assigned to 15 tanks (3 tanks/group). Fish were fed the experimental diet twice daily for 8 weeks. The increased dietary Chlorella meal quadratically influenced the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), and feed intake (FI), which were significantly lower in the C100 group than in the other groups (P < 0.05). The feed conversion ratio (FCR) increased linearly or quadratically with dietary Chlorella meal. Dietary Chlorella meal linearly or quadratically increased the lutein content of plasma, liver, and dorsal muscle of largemouth bass (P < 0.05). Compared to the C0 group, all supplemented Chlorella meal groups significantly improved the yellowness (b∗) of the dorsal body (1.5 to 2.0 fold), abdominal body (1.5 to 1.8 fold), and dorsal muscle (3.8 to 5.4 fold) of largemouth bass (P < 0.05). In addition, compared to the C0 group, the liver vacuolation area of fish was significantly increased in the C75 and C100 groups (P < 0.05). Transcriptional levels of apoptosis-related genes of ß-cell lymphoma-2 (bcl2), caspase-9-like (casp9), and caspase-3a (casp3) were markedly upregulated (0.9 to 1.6 fold) in the C100 group compared to the C0 group (P < 0.05). Based on the quadratic regression analysis between FBW, WGR, or SGR and dietary Chlorella meal level, largemouth bass had the best growth when replacing 31.7% to 32.6% of fish meal with 15.03% to 15.43% dietary Chlorella meal. The present results indicated that dietary supplementation with Chlorella meal (11.85% to 47.45%) significantly enhanced the pigmentation; however, total replacement of fish meal (40%) with Chlorella meal (47.45%) caused growth retardation, apoptosis, and liver damage in largemouth bass.

Environmental enrichment ameliorates high-fat diet induced olfactory deficit and decrease of parvalbumin neurons in the olfactory bulb in mice.

Overweight induced by high-fat diet (HFD) represents one of the major health concerns in modern societies, which can cause lasting peripheral and central metabolic disorders in all age groups. Specifically, childhood obesity could lead to life-long impact on brain development and functioning. On the other hand, environmental enrichment (EE) has been demonstrated to be beneficial for learning and memory. Here, we explored the impact of high-fat diet on olfaction and organization of olfactory bulb cells in adolescent mice, and the effect of EE intervention thereon. Puberty mice (3-week-old) fed with HFD for 10 weeks exhibited poorer odor sensitivity and olfactory memory relative to controls consuming standard chows. The behavioral deficits were rescued in the HFD group with EE intervention. Neuroanatomically, parvalbumin (PV) interneurons in the olfactory bulb (OB) were reduced in the HFD-fed animals relative to control, while EE intervention also normalized this alteration. In contrast, cells expressing calbindin (CB), doublecortin (DCX) in the OB were not altered. Our findings suggest that PV interneurons may play a crucial role in mediating the HFD-induced olfactory deficit in adolescent mice, and can also serve a protective effect of EE against the functional deficit.

Effects of Replacement of Dietary Fishmeal by Cottonseed Protein Concentrate on Growth Performance, Liver Health, and Intestinal Histology of Largemouth Bass (Micropterus salmoides).

An 8-week feeding trial was conducted to explore the effects of replacement of dietary fishmeal by cottonseed protein concentrate (CPC) on growth performance, liver health, and intestine histology of largemouth bass. Four isoproteic and isolipidic diets were formulated to include 0, 111, 222, and 333 g/kg of CPC, corresponding to replace 0% (D1), 25% (D2), 50% (D3), and 75% (D4) of fishmeal. Two hundred and forty largemouth bass (15.11 ± 0.02 g) were randomly divided into four groups with three replicates per group. During the experiment, fish were fed to apparent satiation twice daily. Results indicated that CPC could replace up to 50% fishmeal in a diet for largemouth bass without significant adverse effects on growth performance. However, weight gain rate (WGR), specific growth rate (SGR), feed efficiency (FE), and condition factor (K) of the largemouth bass were significantly decreased when 75% of dietary fishmeal that was replaced by CPC. The whole body lipid content was increased with the increasing of dietary CPC levels. Oil red O staining results indicated that fish fed the D4 diet showed an aggravated fat deposition in the liver. Hepatocytes exhibited serious degeneration, volume shrinkage, and inflammatory cells infiltration in the D4 group. Intestinal villi appeared shorter and sparse with severe epithelial damage in the D4 group. The transcription levels of anti-inflammatory cytokines, such as transforming growth factor ß (tgf-ß), interleukin 10 (il-10), and interleukin 11 ß (il-11ß), were downregulated in the D4 group. The lipid metabolism-related genes carnitine palmitoyl transferase 1 (cpt1), peroxisome proliferator-activated receptor α (pparα), and target of rapamycin (TOR) pathway were also significantly downregulated in the D4 group. It was concluded that suitable replacement of fishmeal by less than 222 g CPC/kg diet had a positive effect on growth performance of fish, but an excessive substitution of 75% fishmeal by CPC would lead to the suppressed growth, liver inflammation, and intestinal damage of largemouth bass.

The Retrotransposition of L1 is Involved in the Reconsolidation of Contextual Fear Memory in Mice.

BACKGROUND: The long interspersed element-1 (L1) participates in memory formation, and DNA methylation patterns of L1 may suggest resilience or vulnerability factors for Post-Traumatic Stress Disorder (PTSD), of which the principal manifestation is a pathological exacerbation of fear memory. However, the unique roles of L1 in the reconsolidation of fear memory remain poorly understood. OBJECTIVE: The study aimed to investigate the role of L1 in the reconsolidation of context-dependent fear memory. METHODS: Mice underwent fear conditioning and fear recall in the observation chambers. Fear memory was assessed by calculating the percentage of time spent freezing in 5 min. The medial prefrontal cortex (mPFC) and hippocampus were removed for further analysis. Open Reading Frame 1 (ORF1) mRNA and ORF2 mRNA of L1 were analyzed by real-time quantitative polymerase chain reaction. After reactivation of fear memory, lamivudine was administered and its effects on fear memory reconsolidation were observed. RESULTS: ORF1 and ORF2 mRNA expressions in the mPFC and hippocampus after recent (24 h) and remote (14 days) fear memory recall exhibited augmentation via different temporal and spatial patterns. Reconsolidation of fear memory was markedly inhibited in mice treated with lamivudine, which could block L1. DNA methyltransferase mRNA expression declined following lamivudine treatment in remote fear memory recall. CONCLUSION: The retrotransposition of L1 participated in the reconsolidation of fear memory after reactivation of fear memory, and with lamivudine treatment, spontaneous recovery decreased with time after recent and remote fear memory recall, providing clues for understanding the roles of L1 in fear memory.

Prognostic and Predictive Value of a 15 Transcription Factors (TFs) Panel for Hepatocellular Carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) is one of the most devastating diseases worldwide. Limited performance of clinicopathologic parameters as prognostic factors underscores more accurate and effective biomarkers for high-confidence prognosis that guide decision-making for optimal treatment of HCC. The aim of the present study was to establish a novel panel to improve prognosis prediction of HCC patients, with a particular interest in transcription factors (TFs). MATERIALS AND METHODS: A TF-related prognosis model of liver cancer with data from ICGC-LIRP-JI cohort successively were processed by univariate and multivariate Cox regression analysis. Then, for evaluating the prognostic prediction value of the model, receiver operating characteristic (ROC) curve and survival analysis were performed both with internal data from the International Cancer Genome Consortium (ICGC) and external data from The Cancer Genome Atlas (TCGA). Furthermore, we verified the expression of three genes in HCC cell lines by Western blot and qPCR and protein expression level by IHC in liver cancer patients' sample. Finally, we constructed a TF clinical characteristics nomogram to furtherly predict liver cancer patient survival probability with TCGA cohort. RESULTS: By Cox regression analysis, a panel of 15 TFs (ZNF331, MYCN, AHRR, LEF1, ZNF780A, POU1F1, DLX5, ZNF775, PLSCR1, FOXK1, TAL2, ZNF558, SOX9, TCFL5, GSC) was identified to present with powerful predictive performance for overall survival of HCC patients based on internal ICGC cohort and external TCGA cohort. A nomogram that integrates these factors was established, allowing efficient prediction of survival probabilities and displaying higher clinical utility. CONCLUSION: The 15-TF panel is an independent prognostic factor for HCC, and 15 TF-based nomogram might provide implication an effective approach for HCC patient management and treatment.

BDNF polymorphisms across the spectrum of psychiatric morbidity: A protocol for a systematic review and meta-analysis.

BACKGROUND: Nowadays, psychiatric morbidities are more and more common, which imposes huge social and economic burden on all countries across the world. Mental illnesses are found to be related to genetics. Over the past few years, a large number of risk genes and loci related to psychiatric morbidities have been reported. The brain-derived neurotrophic factor (BDNF) is one of the main candidates in neuropsychiatric genetics. However, different studies have shown inconsistencies regarding effect modification of BDNF polymorphisms on psychiatric morbidities. Therefore, in the present study, we aim to qualitatively and quantitatively summarize the relationship between BDNF single nucleotide polymorphisms (SNPs) and various psychiatric morbidities through a meta-analysis. METHODS: PubMed, Web of Science and Embase will be searched using a specified search strategy to identify relevant studies up to April 2020. The meta-analysis will be performed on (1) allele model, (2) dominant model, (3) recessive model, (4) homozygote, and (5) heterozygote model. Sensitivity analyses will be conducted to explore the impact of individual studies on the overall result by evaluating the odd ratios (ORs) with their corresponding 95% confidence intervals (CIs) before and after removing each of the studies from our meta-analysis. Chi-square test will be used to determine whether the observed allele or genotype frequencies in the controls are consistent with HWE. The statistical heterogeneity will be verified by I statistics. The fixed effects model is needed to estimate the ORs and 95% CIs when there was no heterogeneity between results of included studies (I < 50%); instead, the random effects model should be used when results of included studies showed significant heterogeneity (I > 50%). Publication bias will be evaluated with the use of Begg test and Egger test (P < .05 is considered statistically significant). DISCUSSION: With this protocol, a methodology is established that explores the effect modification of BDNF polymorphisms on the association with psychiatric morbidities. Findings from this meta-analysis can provide significant insight into the etiology of psychiatric morbidities. REGISTRATION: Open Science Framework (OSF) Preregistration. September 15, 2020. OSF.IO/QS7XT.

Effects of environmental enrichment on cognitive behavior and the expression of adenosine triphosphate binding cassette transporter A7 in hippocampus of adolescent mice with high fat diet. / ä¸°å¯ŒçŽ¯å¢ƒå¯¹é’æ˜¥æœŸé«˜è„‚é¥®é£Ÿå°é¼ è®¤çŸ¥è¡Œä¸ºå’Œæµ·é©¬ä¸‰ç£·é ¸è ºè‹·ç»“åˆç›’è½¬è¿å­A7表达的影响.

OBJECTIVES: To investigate the effects of environmental enrichment on cognitive behavior and the expression of adenosine triphosphate binding cassette transporter A7 (ABCA7) in hippocampus of the adolescent mice with high fat diet. METHODS: A total of healthy 3-week-old male C57BL/6J mice were randomly divided into 3 groups: a control (Con) group, a high fat diet (HFD) group, and a high fat diet+environmental enrichment (HFD+EE) group, with 10 mice in each group. The Con group was given normal diet. The HFD group was given high fat diet. The HFD+EE group was given high fat diet; at the same time, they treated by environmental enrichment. After 10 weeks, open field test was used to detect activity. Novel object recognition test and Y maze test were used to detect cognitive behavior. After the test, the brain was collected and used to detect the protein expression of ABCA7 in the hippocampus by immunohistochemistry and Western blotting. And quantitative RT-PCR (RT-qPCR) was used to detect the ABCA7 mRNA expression level in the hippocampus. RESULTS: There was no significant difference in the total movement distance in the mice among the 3 groups (P>0.05). In the novel object recognition test, the discrimination index of the HFD group was much lower than that of the Con group, and the difference was significant (P<0.01). The discrimination index of the HFD+EE group was higher than that of the HFD group, and the difference was significant (P<0.01). In the Y maze test, there was no significant difference in the percentage of time spent on the new arm among the mice in the 3 groups (P=0.1279). The percentage of entries in new arm in the HFD group was much lower than that in the Con group, and the difference was significant (P<0.01). The percentage of the entries in new arm in the HFD+EE group was significantly higher than that in the HFD group (P<0.05). The results of immunohistochemistry showed that ABCA7 was positively expressed in the cytoplasm of hippocampal neurons in the mice from these 3 groups, and the expression of ABCA7 in the hippocampus of the HFD group was lower than that of the Con group (CA1: P<0.01, CA3: P=0.06), while the expression of ABCA7 in hippocampus of HFD+EE group was higher than that of HFD group (CA1: P=0.23, CA3: P<0.05). Western blotting results showed that compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD group was significantly reduced (P<0.05), while compared with the Con group, the protein level of ABCA7 in the hippocampus of the HFD+EE group showed an upward trend (P=0.06). The results of RT-qPCR showed that the mRNA level of ABCA7 in the hippocampus of HFD group was significantly lower than that of the Con group (P<0.01), while the mRNA level of ABCA7 in the hippocampus of HFD+EE group was significantly higher than that of the HFD group (P<0.01). CONCLUSIONS: High fat diet in adolescent can impair cognitive function with a decrease in the expression of ABCA7 in hippocampus, which can be ameliorate by environmental enrichment.

White matter microstructural alterations in posttraumatic stress disorder: An ROI and whole-brain based meta-analysis.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a debilitating mental illness that is thought to be associated with brain white matter (WM) alterations. Individual diffusion tensor imaging (DTI) studies to date have reported inconsistent alterations in FA across different brain regions in patients with PTSD. Here, we aimed to investigate FA in PTSD using both region-of-interest (ROI)-based and whole-brain-based meta-analytic approaches. OBJECTIVES: Individual ROI-based meta-analysis was carried out in each eligible white matter tract and seed-based D mapping (SDM) meta-analysis was conducted in the whole brain to identify the convergence of FA alterations in PTSD relative to controls. RESULTS: Seventeen studies were included in ROI-based meta-analysis (≥ 3 studies were included for each ROI, NPTSD ≥ 80 and Ncontrol ≥ 103 per ROI). Fourteen studies with a total of 322 PTSD and 335 controls were included in whole-brain based meta-analysis. Both ROI and whole-brain meta-analyses showed that patients with PTSD have significantly higher FA in the inferior fronto-occipital fasciculus and lower FA in the genu of corpus callosum. Whole-brain meta-analyses also identified higher FA in the left inferior temporal gyrus and lower FA in the anterior cingulum and left corticospinal tract. LIMITATIONS: A small number of studies were included in some ROI tracts. Thus the results should be interpreted with caution. CONCLUSIONS: Our results suggest that PTSD patients have increased FA in areas related to visual processing, but decreased FA in anterior brain regions critical to cognition association and fear regulation.

The characteristics of glucose homoeostasis in grass carp and Chinese longsnout catfish after oral starch administration: a comparative study between herbivorous and carnivorous species of fish.

An oral starch administration trial was used to evaluate glucose homoeostasis in grass carp (Ctenopharyngodon idella) and Chinese longsnout catfish (Leiocassis longirostris Günther). Fish were administered with 3 g of a water and starch mixture (with 3:2 ratio) per 100 g body weight after fasting for 48 h. Fish were sampled at 0, 1, 3, 6, 12, 24 and 48 h after oral starch administration. In grass carp, plasma levels of glucose peaked at 3 h but returned to baseline at 6 h. However, in Chinese longsnout catfish, plasma glucose levels peaked at 6 h and returned to baseline at 48 h. The activity of intestinal amylase was increased in grass carp at 1 and 3 h, but no significant change in Chinese longsnout catfish was observed. The activity of hepatic glucose-6-phosphatase fell significantly in grass carp but change was not evident in Chinese longsnout catfish. The expression levels and enzymic activity of hepatic pyruvate kinase increased in grass carp, but no significant changes were observed in the Chinese longsnout catfish. Glycogen synthase (gys) and glycogen phosphorylase (gp) were induced in grass carp. However, there was no significant change in gys and a clear down-regulation of gp in Chinese longsnout catfish. In brief, compared with Chinese longsnout catfish, grass carp exhibited a rapid increase and faster clearance rate of plasma glucose. This effect was closely related to significantly enhanced levels of digestion, glycolysis, glycogen metabolism and glucose-induced lipogenesis in grass carp, as well as the inhibition of gluconeogenesis.

Acute restraint stress alters food-foraging behavior in rats: Taking the easier Way while suffered.

Stress can influence decision-making in humans from many cognitive perspectives, while the underlying neurobiological mechanism remains incompletely understood. Food-foraging is a rodent behavior involving strategic possessing of nutritional supply in social context; experimental model of this behavior could help explore the effect of stress on decision-making and the brain mechanism thereof. In the present study, the influence of stress on food-foraging behavior was assessed in rats using an open field choosing paradigm wherein food collection (standard food or sweet food) were associated with social competition (with or without a rat in the cage). Acute restraint stress (ARS) was induced by placing the rat in a plastic restrainer for 2 h before food-foraging behavioral tests, with the effect of stress also determined biochemically and immunohistochemically. Restraint stressed rats showed anxiety-like behavior and elevation of serum corticosterone (CORT) and epinephrine (EPI) relative to controls. Both restraint and control animals preferred sugared food. However, the former group tended to forage food from a cage not occupied by a conspecific rat, whereas the control rats preferred to obtain food from the cage with a social competitor. Thus, the total amount of food foraged and eaten are reduced in the restrained rats than in controls. While the restraint animals had normal social interaction with other rats, they displayed enhanced social agonistic behavior. In brain examination, ARS attenuated the increase in immunolabeling and protein levels of c-fos, p-CREB, p-ERK1/2 in the anterior cingulate cortex (ACC) observed in control animals in association with food-foraging. These results indicate that restraint stressed rats tend to forage food by taking the advantage of a less competitive opportunity. Mechanistically, this decision-making alternative appears to be mediated through a neuronal deactivation in the ACC. The current findings provide novel insights into neuronal processing of decision-making behavior under the influence of stress.

Different roles of insulin receptor a and b in maintaining blood glucose homeostasis in zebrafish.

An inability of insulin to signal glycolysis and gluconeogenesis would largely result in type 2 diabetes. In this study, the physiological roles of zebrafish insulin receptor a and b in maintaining blood glucose homeostasis were characterized. We observed that, though blood glucose in insra-/- fish and insrb-/- fish were comparable with the control siblings at 0 h postprandium (hpp), the most evident hyperglycemia have been observed in insra-/- fish from 1 hpp to 3 hpp. A mild increase of blood glucose in insrb-/- fish has been seen only at 1.5 hpp. The down-regulated expressions of glycolytic enzymes were observed in insra-/- fish and insrb-/- fish liver and muscle, together with the significantly decreased activities or concentrations of glycolytic enzymes. These results suggest that both Insra and Insrb were critical in glycolysis. Intriguingly, the up-regulated expressions of gluconeogenic enzymes, pck1 and g6pca.1, along with the elevated enzyme activities, were observed in insra-/- fish liver at 1 hpp and 1.5 hpp. Compared with the control fish, the elevated plasma insulin and lowered phosphorylated AKT were observed in insra-/- fish and insrb-/- fish, suggesting that there is an insulin resistance in insra-/- fish and insrb-/- fish. The increased levels of both transcriptions of foxo1a and Foxo1a protein abundance in the insra-/- fish liver have been found. When insra-/- fish treated with the Foxo1 inhibitor, the postprandial blood glucose levels could be normalized, accompanied with the normalized expression levels and enzyme activities of both pck1 and g6pca.1. Therefore, Insra and Insrb demonstrate a similar role in promoting glycolysis, but Insra is involved in inhibiting gluconeogenesis via down-regulating the expression of foxo1a. Our results indicate that Insra and Insrb exhibit diversified functions in maintaining glucose homeostasis in zebrafish.

Different physiological roles of insulin receptors in mediating nutrient metabolism in zebrafish.

Insulin, the most potent anabolic hormone, is critical for somatic growth and metabolism in vertebrates. Type 2 diabetes, which is the primary cause of hyperglycemia, results from an inability of insulin to signal glycolysis and gluconeogenesis. Our previous study showed that double knockout of insulin receptor a ( insra) and b ( insrb) caused ß-cell hyperplasia and lethality from 5 to 16 days postfertilization (dpf) (Yang BY, Zhai G, Gong YL, Su JZ, Han D, Yin Z, Xie SQ. Sci Bull (Beijing) 62: 486-492, 2017). In this study, we characterized the physiological roles of Insra and Insrb, in somatic growth and fueling metabolism, respectively. A high-carbohydrate diet was provided for insulin receptor knockout zebrafish from 60 to 120 dpf to investigate phenotype inducement and amplification. We observed hyperglycemia in both insra-/- fish and insrb-/- fish. Impaired growth hormone signaling, increased visceral adiposity, and fatty liver were detected in insrb-/- fish, which are phenotypes similar to the lipodystrophy observed in mammals. More importantly, significantly diminished protein levels of P-PPARα, P-STAT5, and IGF-1 were also observed in insrb-/- fish. In insra-/- fish, we observed increased protein content and decreased lipid content of the whole body. Taken together, although Insra and Insrb show overlapping roles in mediating glucose metabolism through the insulin-signaling pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis through activation of the growth hormone-signaling pathway, whereas Insra primarily acts to promote lipid synthesis via glucose utilization.

Effects of dietary Tenebrio molitor meal on the growth performance, immune response and disease resistance of yellow catfish (Pelteobagrus fulvidraco).

This study evaluated the influence of diets containing mealworm (Tenebrio molitor) meal in partial substitution of fishmeal on growth performance and immune responses of juvenile yellow catfish (Pelteobagrus fulvidraco). Four diets were formulated to contain 0 (the control diet), 9, 18 and 27 g mealworm meal per 100 g diet with 0%, 25%, 50% and 75% of fishmeal replacement, respectively. Yellow catfish were randomly divided into 4 groups with 3 replicates in each group. The fish in each group were fed with one of the four experimental diets for 5 weeks. Growth performance, plasma parameters (SOD, MDA, IgM, C3, lysozyme) and immune related genes (MHC II, IL-1, CypA, IgM, HE) of yellow catfish were determined at the end of the feeding trial, as well as 24 h post bacterial (Edwardsiella ictaluri) challenge. The present results showed that dietary inclusion of mealworm meal (MW) had no negative effects on the growth performance of the juvenile yellow catfish, compared to the control group. At the end of the feeding trial, plasma MDA contents of MW supplemented groups were significant lower than the control group. Plasma SOD activities increased significantly with the increasing dietary MW contents at the end of feeding trial (pre-challenge) and 24 h post challenge with E. ictaluri. Significant increase of plasma lysozyme activity was found in MW supplemented groups compared to the control group 24 h post bacterial challenge. Plasma IgM levels increased significantly with the increasing dietary MW contents at the end of feeding trial. Compared with the control group, the immune related genes of MHC II, IL-1, IgM and HE of the fish in the MW supplemented groups significantly upregulated pre-challenge or 24 h post bacterial challenge. Finally, it was observed that the survival rate of the 27% MW group was significant higher (P < 0.05) than the control group but was not significantly differed from the 18% MW group. The present results indicated that dietary inclusion level of at least 18% MW could improve the immune response and the bacterial resistance of yellow catfish without any negative growth effects.

Consecutive record-breaking high temperatures marked the handover from hiatus to accelerated warming.

Closely following the hiatus warming period, two astonishing high temperature records reached in 2014 and 2015 consecutively. To investigate the occurrence features of record-breaking high temperatures in recent years, a new index focusing the frequency of the top 10 high annual mean temperatures was defined in this study. Analyses based on this index shown that record-breaking high temperatures occurred over most regions of the globe with a salient increasing trend after 1960 s, even during the so-called hiatus period. Overlapped on the ongoing background warming trend and the interdecadal climate variabilities, the El Niño events, particularly the strong ones, can make a significant contribution to the occurrence of high temperatures on interannual timescale. High temperatures associated with El Niño events mainly occurred during the winter annual period. As the Pacific Decadal Oscillation (PDO) struggled back to its positive phase since 2014, the global warming returned back to a new accelerated warming period, marked by the record-breaking high temperatures in 2014. Intensified by the super strong El Niño, successive high records occurred in 2015 and 2016. Higher frequencies of record high temperatures would occur in the near future because the PDO tends to maintain a continuously positive phase.

Depletion of insulin receptors leads to ß-cell hyperplasia in zebrafish.

Hyperglycemia in type 2 diabetes results from an inability of insulin to regulate gluconeogenesis. To characterize the role of the insulin/insulin receptor pathway in glycometabolism and type 2 diabetes, we created a zebrafish model in which insulin receptors a and b (insra and insrb) have been ablated. We first observed that insra and insrb were both expressed abundantly during embryonic development and in various adult tissues. Increased expression of insulin and number of ß-cells were observed in insra-/-/insrb-/- fish together with higher glucose in insra-/-, insrb-/-, or insra-/-/insrb-/- fish, indicating that insra and insrb were knocked out effectively. However, compared to the wild-type fish, insra-/-/insrb-/- fish died between 5 and 16days post-fertilization (dpf) with severe pericardial edema and increased level of cell apoptosis, which was not induced by increased total body glucose content. Increased gluconeogenesis and decreased glycolysis were also observed in both single and double knockout fish, but no mortality or malformation was observed in single knockout fish. Given the importance of insulin receptors in glucose homeostasis and embryonic development, transcriptome analysis was used to provide an important model of defective insulin signaling and to study its developmental consequences in zebrafish. The results indicated that both insra and insrb played a pivotal role in glucose metabolism and embryonic development, and insra was more critical than insrb in the insulin signaling pathway.