Publications by authors named "Fang Qiao"

68 Publications

ameliorates high-carbohydrate diet-induced metabolic phenotypes by restoration of intestinal acetate-producing bacteria in Nile Tilapia.

Br J Nutr 2021 Apr 16:1-13. Epub 2021 Apr 16.

School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.

Poor utilisation efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD)-induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), HCD or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. High-throughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.
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http://dx.doi.org/10.1017/S0007114521001318DOI Listing
April 2021

Proteomic analysis reveals the protective role of exogenous hydrogen sulfide against salt stress in rice seedlings.

Nitric Oxide 2021 Jun 8;111-112:14-30. Epub 2021 Apr 8.

Key Laboratory for Subtropical Wetland Ecosystem Research of MOE, College of the Environment and Ecology, Xiamen University, Xiamen, Fujian, 361005, PR China. Electronic address:

Hydrogen sulfide (HS) is an important gaseous signal molecule which participates in various abiotic stress responses. However, the underlying mechanism of HS associated salt tolerance remains elusive. In this study, sodium hydrosulfide (NaHS, donor of HS) was used to investigate the protective role of HS against salt stress at the biochemical and proteomic levels. Antioxidant activity and differentially expressed proteins (DEPs) of rice seedlings treated by NaCl or/and exogenous HS were investigated by the methods of biochemical approaches and comparative proteomic analysis. The protein-protein interaction (PPI) analysis was used for understanding the interaction networks of stress responsive proteins. In addition, relative mRNA levels of eight selected identified DEPs were analyzed by quantitative real-time PCR. The result showed that HS alleviated oxidative damage caused by salt stress in rice seedling. The activities of some antioxidant enzymes and glutathione metabolism were mediated by HS under salt stress. Proteomics analyses demonstrated that NaHS regulated antioxidant related proteins abundances and affected related enzyme activities under salt stress. Proteins related to light reaction system (PsbQ domain protein, plastocyanin oxidoreductase iron-sulfur protein), Calvin cycle (phosphoglycerate kinase, sedoheptulose-1,7-bisphosphatase precursor, ribulose-1,5-bisphosphate carboxylase/oxygenase) and chlorophyll biosynthesis (glutamate-1-semialdehyde 2,1-aminomutase, coproporphyrinogen III oxidase) are important for NaHS against salt stress. ATP synthesis related proteins, malate dehydrogenase and 2, 3-bisphosphoglycerate-independent phosphoglycerate mutase were up-regulated by NaHS under salt stress. Protein metabolism related proteins and cell structure related proteins were recovered or up-regulated by NaHS under salt stress. The PPI analysis further unraveled a complicated regulation network among above biological processes to enhance the tolerance of rice seedling to salt stress under HS treatment. Overall, our results demonstrated that HS takes protective roles in salt tolerance by mitigating oxidative stress, recovering photosynthetic capacity, improving primary and energy metabolism, strengthening protein metabolism and consolidating cell structure in rice seedlings.
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http://dx.doi.org/10.1016/j.niox.2021.04.002DOI Listing
June 2021

Influences of dietary vitamin D on growth, antioxidant capacity, immunity and molting of Chinese mitten crab (Eriocheir sinensis) larvae.

J Steroid Biochem Mol Biol 2021 Jun 3;210:105862. Epub 2021 Mar 3.

Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai, 200241, PR China. Electronic address:

This study investigates the effects of vitamin D (VD) on growth performance, antioxidant capacity, immunity and molting of larval Chinese mitten crab Eriocheir sinensis. A total of 6,000 larvae (7.52 ± 0.10 mg) were fed with six isonitrogenous and isolipidic experimental diets with different levels of dietary VD (0, 3000, 6000, 9000, 12000 and 36000 IU/kg) respectively for 23 days. The highest survival and molting frequency were found in crabs fed 6000 IU/kg VD. Weight gain, specific growth rate, and carapace growth significantly increased in crabs fed 3000 and 6000 IU/kg VD compared to the control. Broken-line analysis of molting frequency, weight gain and specific growth rate against dietary VD levels indicates that the optimal VD requirement for larval crabs is 4825-5918 IU/kg. The highest whole-body VD content occurred in the 12000 IU/kg VD group, and the 25-dihydroxy VD content decreased with the increase of dietary VD. The malonaldehyde content was lower than the control. Moreover, the superoxide dismutase activity, glutathione peroxidase and total antioxidant capacity of crab fed 6000 IU/kg VD were significantly higher than in control. Crabs fed 9000 IU/kg showed the highest survival after 120 h of salinity stress, and the relative mRNA expressions indicate vitamin D receptor (VDR) is the important regulatory element in molting and innate immunity. The molting-related gene expressions showed that the response of crab to salinity was self-protective. This study would contribute to a new understanding of the molecular basis underlying molting and innate immunity regulation by vitamin D in E. sinensis.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105862DOI Listing
June 2021

Alleviation of the Adverse Effect of Dietary Carbohydrate by Supplementation of -Inositol to the Diet of Nile Tilapia ().

Animals (Basel) 2020 Nov 23;10(11). Epub 2020 Nov 23.

Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai 200241, China.

This study investigated the effect of dietary -inositol (MI) on alleviating the adverse effect of the high carbohydrate diet in Nile tilapia (). Six diets contained either low carbohydrate (LC 30%) or high carbohydrate (HC 45%) with three levels of MI supplementation (0, 400 and 1200 mg/kg diet) to each level of the carbohydrate diet. After an 8-week trial, the fish fed 400 mg/kg MI under HC levels had the highest weight gain and fatness, but the fish fed 1200 mg/kg MI had the lowest hepatosomatic index, visceral index and crude lipid in the HC group. The diet of 1200 mg/kg MI significantly decreased triglyceride content in the serum and liver compared with those fed the MI supplemented diets regardless of carbohydrate levels. Dietary MI decreased triglyceride accumulation in the liver irrespective of carbohydrate levels. The content of malondialdehyde decreased with increasing dietary MI at both carbohydrate levels. Fish fed 1200 mg/kg MI had the highest glutathione peroxidase, superoxide dismutase, aspartate aminotransferase and glutamic-pyruvic transaminase activities. The HC diet increased the mRNA expression of key genes involved in lipid synthesis () in the fish fed the diet without MI supplementation. Dietary MI significantly under expressed fatty acid synthetase in fish fed the HC diets. Moreover, the mRNA expression of genes related to lipid catabolism () was significantly up-regulated with the increase of dietary MI levels despite dietary carbohydrate levels. The gene expressions of gluconeogenesis, glycolysis and MI biosynthesis were significantly down-regulated, while the expression of the pentose phosphate pathway was up-regulated with the increase of MI levels. This study indicates that HC diets can interrupt normal lipid metabolism and tend to form a fatty liver in fish. Dietary MI supplement can alleviate lipid accumulation in the liver by diverging some glucose metabolism into the pentose phosphate pathway and enhance the antioxidant capacity in .
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http://dx.doi.org/10.3390/ani10112190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700398PMC
November 2020

The individual and combined effects of hypoxia and high-fat diet feeding on nutrient composition and flesh quality in Nile tilapia (Oreochromis niloticus).

Food Chem 2021 May 28;343:128479. Epub 2020 Oct 28.

LANEH, School of Life Sciences, East China Normal University, Shanghai 200241, PR China. Electronic address:

Hypoxia and high-fat diet (HFD) feeding are two factors commonly existing in aquaculture. However, their individual and combined effects on nutrient composition and flesh quality in fish have not been investigated. The present study evaluated the alterations of growth, nutrient composition and flesh quality in Nile tilapia (initially 7.0 ± 0.1 g and 5.6 ± 0.2 cm) fed with normal fat diet (5.95% fat) or HFD (11.8% fat) at two dissolved oxygen levels (1.1 ± 0.1 and 7.2 ± 0.1 mg/L) for 8 weeks. The results showed that hypoxia and HFD had similar effects in inducing lipid deposition, reducing flesh protein and amino acids content, pH values and water holding ability. Hypoxia had additional adverse effects in decreasing meat yield, flesh contents of n-3 PUFA and glycogen, increasing flesh fragmentation and causing liver damages. The combination of hypoxia and HFD significantly decreased feed intake, survival rate and muscle protein content, but didn't affect flesh quality-related parameters.
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http://dx.doi.org/10.1016/j.foodchem.2020.128479DOI Listing
May 2021

First report of powdery mildew of crape jasmine () caused by in China.

Plant Dis 2020 Oct 13. Epub 2020 Oct 13.

Shenzhen Polytechnic, 47891, Shenzhen, Guangdong, China;

Crape jasmine (Tabernaemontana divaricata) is a popular flowering shrub widely grown in southern China. Its leaves and roots are used in Chinese traditional medicine. In December, 2019, powdery mildew symptoms were observed on five crape jasmine shrubs on the campus of Shenzhen Polytechnic (22°35'N; 113°56'E), in Guangdong province. Approximately 45% of leaves were infected. Symptoms initially appeared as circular to irregular white patches on the leaf petiole, and subsequently coalesced to develop into abundant hyphal growth on both sides of the leaves, which soon wilted. Hyphae were septate, branched, with simple kidney-shaped to moderately lobed appressoria. Conidia formed singly, ellipsoid-ovoid to subcylindrical, 27-37 × 14-20 μm (mean 32±2.5 × 17±1.6 μm), with a length/width ratio varying from 1.3 to 2.4. Conidiophores were erect, unbranched, consisted of two cells, 60 to 84 μm long (mean 73±4 μm), and with straight to severely kinked cylindrical foot-cells at the base, 29-35 × 3-7 μm (mean 32±3 × 6±2 μm). Chasmothecia were not observed on sampled plants. These morphological characteristics were typical to the conidial stage of the genus Erysiphe (Braun and Cook, 2012). For molecular identification, genomic DNA was extracted from conidia washed from infected leaves and using Fungal DNA Kit (Omega Bio-tek Inc., Guangzhou, China). Semi-nested PCR amplification of the internal transcribed spacer (ITS) region of rDNA was conducted by using primer sets P3 (Kusaba et al., 1995)/ITS5 and ITS5/ITS4 (White et al., 1990) for the first and second reactions, respectively. BLASTn analysis of the obtained 719 bp sequence (GenBank Accession No. MT802112) showed 99.7% identity with those of E. elevata (KY660910, MH985631, MK253282). On the basis of morphological and molecular analyses, the fungus was identified as Erysiphe elevata. To confirm pathogenicity, infected leaves were gently pressed onto healthy leaves of three healthy plants in separate pots, and three noninoculated plants were used as controls. All plants were maintained in a greenhouse at 25 ℃, and relative humidity of 50 to 65%. After 11 days, similar disease symptoms were observed on the inoculated plants while no symptoms developed on control plants. The fungus observed on the inoculated shrubs was identical morphologically to that o the original infected leaves. E. elevata is a common powdery mildew species infecting Catalpa spp. (Cook et al., 2006), Plumeria rubra (Wu et al., 2019; Yeh et al., 2019) and Eucalyptus camaldulensis (Meeboon and Takamatsu, 2017). However, no powdery mildew were found on P. rubra nearby. To our knowledge, this is the first report of this fungus infecting T. divaricata.
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http://dx.doi.org/10.1094/PDIS-08-20-1717-PDNDOI Listing
October 2020

Inulin alleviates adverse metabolic syndrome and regulates intestinal microbiota composition in Nile tilapia () fed with high-carbohydrate diet.

Br J Nutr 2021 Jul 13;126(2):161-171. Epub 2020 Oct 13.

Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), College of Life Sciences, East China Normal University, Shanghai200241, People's Republic of China.

A high-carbohydrate diet could achieve a protein-sparing effect, but it may cause negative impacts on the growth condition of fish due to their poor utilisation ability of carbohydrate. How to reduce the adverse effects caused by a high-carbohydrate diet is important for the development of aquaculture. In the present study, we aimed to identify whether inulin could attenuate the metabolic syndrome caused by a high-carbohydrate diet in fish. Nile tilapia (Oreochromis niloticus) (1·19 (sd 0·01) g) were supplied with 35 % carbohydrate (CON), 45 % carbohydrate (HC) and 45 % carbohydrate + 5 g/kg inulin (HCI) diets for 10 weeks. The results showed that addition of inulin improved the survival rate when fish were challenged with Aeromonas hydrophila, indicating that inulin had an immunostimulatory effect. Compared with the HC group, the HCI group had lower lipid accumulation in liver and the gene expression analyses indicated that addition of inulin down-regulated genes related to lipogenesis and up-regulated genes relevant to β-oxidation significantly (P < 0·05). Higher liver glycogen and glucose tolerance were found in the HCI group compared with the HC group (P < 0·05). These results indicated that inulin could alleviate the metabolic syndrome induced by a high-carbohydrate diet. Furthermore, addition of inulin to a high-carbohydrate diet changed the intestinal bacterial composition and significantly increased the concentration of acetic acid and propionic acid in fish gut which have the potential to increase pathogen resistance and regulate metabolic characteristics in fish. Collectively, our results demonstrated a possible causal role for the gut microbiome in metabolic improvements induced by inulin in fish.
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http://dx.doi.org/10.1017/S000711452000402XDOI Listing
July 2021

Effects of dietary T-2 toxin on gut health and gut microbiota composition of the juvenile Chinese mitten crab (Eriocheir sinensis).

Fish Shellfish Immunol 2020 Nov 14;106:574-582. Epub 2020 Aug 14.

Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, 500 Dongchuan Rd, Shanghai, 200241, China. Electronic address:

The current study aims to investigate the effects of dietary T-2 toxin on the intestinal health and microflora in the juvenile Chinese mitten crab (Eriocheir sinensis) with an initial weight 2.00 ± 0.05 g. Juvenile crabs were fed with experimental diets supplemented with T-2 toxin at 0 (control), 0.6 (T1 group), 2.5 (T2 group) and 5.0 (T3 group) mg/kg diet for 8 weeks. Dietary T-2 toxin increased the malondialdehyde (MDA) content and the expression of Kelch-like ECH-associated protein 1 (keap1) gene while the expression of cap 'n' collar isoform C (CncC) decreased in the intestine. The activities of glutathione peroxidase (GSH-Px) and total anti-oxidation capacity (T-AOC) in the intestine increased only in the lower dose of dietary T-2. Dietary T-2 toxin significantly increased the mRNA expression of caspase-3, caspase-8, Bax and mitogen-activated protein kinase (MAPK) genes and the ratio of Bax to Bcl-2 accompanied with a reduction of Bcl-2 expression. Furthermore, T-2 toxin decreased the mRNA levels of antimicrobial peptides (AMPs), peritrophic membrane (PM1 and PM2) and immune regulated nuclear transcription factors (Toll-like receptor: TLR, myeloid differentiation primary response gene 88: Myd88, relish and lipopolysaccharide-induced TNF-α factor: LITAF). The richness and diversity of the gut microbiota were also affected by dietary T-2 toxin in T3 group. The similar dominant phyla in the intestine of the Chinese mitten crab in the control and T3 groups were found including Bacteroidetes, Firmicutes, Tenericutes and Proteobacteria. Moreover, the inclusion of dietary T-2 toxin of 4.6 mg/kg significantly decreased the richness of Bacteroidetes and increased the richness of Firmicutes, Tenericutes and Proteobacteria in the intestine. At the genus level, Dysgonomonas and Romboutsia were more abundant in T3 group than those in the control. However, the abundances of Candidatus Bacilloplasma, Chryseobacterium and Streptococcus in T3 group were lower than those in the control. This study indicates that T-2 toxin could cause oxidative damage and immunosuppression, increase apoptosis and disturb composition of microbiota in the intestine of Chinese mitten crab.
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http://dx.doi.org/10.1016/j.fsi.2020.08.019DOI Listing
November 2020

Peroxisomal proliferator-activated receptor α-b deficiency induces the reprogramming of nutrient metabolism in zebrafish.

J Physiol 2020 10 7;598(20):4537-4553. Epub 2020 Aug 7.

LANEH, School of Life Sciences, East China Normal University, Shanghai, China.

Key Points: The pparab subtype in zebrafish is much more highly expressed in tissues with high oxidative activity than pparaa. The pparab deficiency in zebrafish reduces fatty acid β-oxidation both in liver and muscle, illustrating its functional homology as a mammalian peroxisome proliferator-activated receptor α (PPARα). pparab deficiency promotes metabolic reprogramming by increasing glucose utilization and inhibiting amino acid breakdown. The present study brings new insights into the comprehensive regulatory roles of PPARα in the cellular fuel selection and provides a valuable animal model for PPARα studies from a viewpoint of comparative physiology.

Abstract: Dysfunction of lipid metabolism is involved in the pathogenesis of several chronic metabolic diseases. Peroxisome proliferator-activated receptor α (PPARα) is essential for normal metabolic homeostasis and, in particular, for the regulation of fatty acid β-oxidation (FAO). However, little is known about its regulation roles in systemic nutrient metabolism. To explore the underlying modulation role of PPARα in metabolic homeostasis, we generated a pparab-knockout zebrafish (Danio rerio) model. The pparab mutants demonstrated lower expression of key enzymes involved in FAO, as well as lower mitochondrial and peroxisomal FAO in tissues, which was associated with lipid accumulation in liver and visceral mass. Conversely, glucose utilization was higher because they demonstrated lower blood glucose and tissue glycogen concentrations, as well as activation of the phosphoinositide 3-kinase/AKT pathway. In addition, pparab-deficient zebrafish demonstrated activation of AKT/mammalian target of rapamycin signalling and higher protein content, implying greater protein synthesis and/or lower amino acid breakdown. These data clearly revealed that pparab deletion reduces FAO but increases glucose utilization and protein deposition to maintain energy homeostasis. The present study provides new insights into the comprehensive regulatory role of PPARα in systemic energy metabolism in fish, and this pparab-deficient zebrafish also constitutes a valuable model for investigating the functions of PPARα in mammals from comparative physiology aspects.
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http://dx.doi.org/10.1113/JP279814DOI Listing
October 2020

Gemfibrozil improves lipid metabolism in Nile tilapia Oreochromis niloticus fed a high-carbohydrate diet through peroxisome proliferator activated receptor-α activation.

Gen Comp Endocrinol 2020 09 12;296:113537. Epub 2020 Jun 12.

Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, 500 Dongchuan Rd, Shanghai 200241, China. Electronic address:

High carbohydrate diet (HCD) can induce lipid metabolism disorder, characterized by excessive lipid in farmed fish. Peroxisome proliferator activated receptor-α (PPARα) plays an important role in lipid homeostasis. In this study, we hypothesize that PPARα can improve lipid metabolism in fish fed HCD. Fish (3.03 ± 0.11 g) were fed with three diets: control (30% carbohydrate), HCD (45% carbohydrate) and HCG (HCD supplemented with 200 mg/kg gemfibrozil, an agonist of PPARα) for eight weeks. The fish fed HCG had higher growth rate and protein effiency than those fed the HCD diet, whereas the opposite trend was observed in feed conversion ratio, hepatosomatic index and mesenteric fat index. Additionally, fish fed HCG significantly decreased lipid accumulation in the whole body, liver and adipose tissues compared to those fed the HCD diet. Furthermore, fish in the HCG group significantly increased the mRNA and protein expression and protein dephosphorylation of PPARα. The HCG group also significantly increased the mRNA level of the downstream target genes of PPARα, whereas the opposite trend occured in the mRNA level of lipolysis-related genes compared to the HCD group. Besides, fish in the HCG group remarkably decreased the contents of alanine aminotransferase, aspartate aminotransferase and malondialdehyde, whereas the opposite occured in the activities of antioxidative enzymes and anti-inflammatory cytokine genes compared to the HCD group. This study indicates that gemfibrozil can improve lipid metabolism and maintain high antioxidant and anti-inflammatory capacity through activating PPARα in Nile tilapia fed a high carbohydrate diet.
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http://dx.doi.org/10.1016/j.ygcen.2020.113537DOI Listing
September 2020

Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer.

Cell 2020 04;181(2):442-459.e29

Department of Inflammation and Oncology and Genome Analysis Unit, Amgen Research, Amgen Inc., South San Francisco, CA 94080, USA. Electronic address:

Single-cell RNA sequencing (scRNA-seq) is a powerful tool for defining cellular diversity in tumors, but its application toward dissecting mechanisms underlying immune-modulating therapies is scarce. We performed scRNA-seq analyses on immune and stromal populations from colorectal cancer patients, identifying specific macrophage and conventional dendritic cell (cDC) subsets as key mediators of cellular cross-talk in the tumor microenvironment. Defining comparable myeloid populations in mouse tumors enabled characterization of their response to myeloid-targeted immunotherapy. Treatment with anti-CSF1R preferentially depleted macrophages with an inflammatory signature but spared macrophage populations that in mouse and human expresses pro-angiogenic/tumorigenic genes. Treatment with a CD40 agonist antibody preferentially activated a cDC population and increased Bhlhe40 Th1-like cells and CD8 memory T cells. Our comprehensive analysis of key myeloid subsets in human and mouse identifies critical cellular interactions regulating tumor immunity and defines mechanisms underlying myeloid-targeted immunotherapies currently undergoing clinical testing.
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http://dx.doi.org/10.1016/j.cell.2020.03.048DOI Listing
April 2020

MiR-155-5p plays as a "janus" in the expression of inflammatory cytokines induced by T-2 toxin.

Food Chem Toxicol 2020 Jun 30;140:111258. Epub 2020 Mar 30.

National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China; MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China. Electronic address:

Although many studies have shown that inflammatory response plays a crucial role in the various toxic effects of T-2 toxin, there are relatively few reports on the mechanism of this phenomenon. Meanwhile, accumulating evidence has shown that miR-155-5p is activated in the inflammatory response. As molecular pathways and mechanisms involved in T-2 toxin-induced inflammatory response are poorly elucidated, we assessed whether miR-155-5p is involved in the inflammation effects mediated by T-2 toxin. Treatment of RAW264.7 cells with T-2 toxin (14 nM and 12 h) resulted in inflammatory response and associated with alteration of the gene expression signature of miR-155-5p. Knockdown or overexpression of miR-155-5p both indicated that miR-155-5p positively regulated the expression of the inflammation factors. Moreover, bioinformatics prediction and luciferase assay indicated that atg3 and rheb are targets of miR-155-5p. However, atg3 and SOCS1 play positive roles in the inflammatory response regulated by miR-155-5p, while rheb plays a negative role. In addition, the in vivo study showed that single administration of T-2 toxin in mice enhances spleen immune response, which was accompanied by an overexpression of miR-155-5p. These findings indicate that miR-155-5p might have an important role associated with the inflammatory response induced by T-2 toxin. In conclusion, a dual character of miR-155-5p in inflammation response was revealed, which might exist in other reactions in which miR-155-5p is involved.
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http://dx.doi.org/10.1016/j.fct.2020.111258DOI Listing
June 2020

Environmental estrogen exposure converts lipid metabolism in male fish to a female pattern mediated by AMPK and mTOR signaling pathways.

J Hazard Mater 2020 07 20;394:122537. Epub 2020 Mar 20.

LANEH, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address:

Environmental estrogens, including bisphenol A (BPA) and 17β-estradiol (E2), which are widely used in industries and medicine, pose a severe ecological threat to fish due to feminization induction. However, the related metabolic basis for reproductive feminization in male fish has not been well addressed. We first found that female zebrafish exhibited higher lipid accumulation and lipogenesis activity than males. Next, we exposed male and female zebrafish to E2 (200 ng/L) or BPA (100 μg/L) for six weeks, and observed an early-phase reproductive feminization in males, accompanied with reduced spermatids, significant fat deposition and lipogenic gene expressions that mimicked female patterns. Cellular signaling assays revealed that, E2 or BPA modulated lipid metabolism in males mainly through lowering 5' AMP-activated protein kinase (AMPK) and upregulating the lipogenic mechanistic target of rapamycin (mTOR) pathways. For the first time, we show that environmental estrogens could alter lipid metabolism in male fish to a female pattern (metabolic feminization) prior to gonad feminization in male fish, to allows males to accumulate efficiently lipids to harmonize with the feminized gonads. This study suggests that negative effects of environmental estrogens, as hazardous materials, on vertebrate health are more complicated than originally thought.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122537DOI Listing
July 2020

Functional differences between l- and d-carnitine in metabolic regulation evaluated using a low-carnitine Nile tilapia model.

Br J Nutr 2019 09 14;122(6):625-638. Epub 2019 Aug 14.

LANEH, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.

l-Carnitine is essential for mitochondrial β-oxidation and has been used as a lipid-lowering feed additive in humans and farmed animals. d-Carnitine is an optical isomer of l-carnitine and dl-carnitine has been widely used in animal feeds. However, the functional differences between l- and d-carnitine are difficult to study because of the endogenous l-carnitine background. In the present study, we developed a low-carnitine Nile tilapia model by treating fish with a carnitine synthesis inhibitor, and used this model to investigate the functional differences between l- and d-carnitine in nutrient metabolism in fish. l- or d-carnitine (0·4 g/kg diet) was fed to the low-carnitine tilapia for 6 weeks. l-Carnitine feeding increased the acyl-carnitine concentration from 3522 to 10 822 ng/g and alleviated the lipid deposition from 15·89 to 11·97 % in the liver of low-carnitine tilapia. However, as compared with l-carnitine group, d-carnitine feeding reduced the acyl-carnitine concentration from 10 822 to 5482 ng/g, and increased lipid deposition from 11·97 to 20·21 % and the mRNA expression of the genes involved in β-oxidation and detoxification in the liver. d-Carnitine feeding also induced hepatic inflammation, oxidative stress and apoptosis. A metabolomic investigation further showed that d-carnitine feeding increased glycolysis, protein metabolism and activity of the tricarboxylic acid cycle and oxidative phosphorylation. Thus, l-carnitine can be physiologically utilised in fish, whereas d-carnitine is metabolised as a xenobiotic and induces lipotoxicity. d-Carnitine-fed fish demonstrates increases in peroxisomal β-oxidation, glycolysis and amino acid degradation to maintain energy homeostasis. Therefore, d-carnitine is not recommended for use in farmed animals.
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http://dx.doi.org/10.1017/S000711451900148XDOI Listing
September 2019

Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis.

Genome Biol 2019 12 31;21(1). Epub 2019 Dec 31.

BIOPIC, Beijing Advanced Innovation Center for Genomics, and School of Life Sciences, Peking University, Beijing, China.

Background: Tumor-reactive CD8+ tumor-infiltrating lymphocytes (TILs) represent a subtype of T cells that can recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated.

Results: In this study, we segregate tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirms previous conclusions that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identifies a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers CD39 and CD103 being specifically demethylated. In addition, dynamic changes are observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor binding motif enrichment analysis identifies several immune-related transcription factors, including three exhaustion-related genes (NR4A1, BATF, and EGR2) and VDR, which potentially play an important regulatory role in tumor-reactive CD8+ T cells.

Conclusion: Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.
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http://dx.doi.org/10.1186/s13059-019-1921-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937914PMC
December 2019

High-carbohydrate diet promotes the adaptation to acute hypoxia in zebrafish.

Fish Physiol Biochem 2020 Apr 9;46(2):665-679. Epub 2019 Dec 9.

LANEH, School of Life Sciences, East China Normal University, Shanghai, 200241, People's Republic of China.

Oxygen deprivation (hypoxia) is a common challenge in water environment, which causes lack of energy and oxidative damage in organisms. Many studies have indicated a number of physiological and metabolic changes under hypoxia, but the effects of dietary nutrients on hypoxia tolerance have not been well evaluated. In the present 7-week feeding trial, we fed zebrafish with low-protein diet (LP), high-protein diet (HP), low-fat diet (LF), high-fat diet (HF), low-carbohydrate diet (LC), and high-carbohydrate diet (HC), respectively. Afterward, the resistance to acute hypoxia challenge, growth, body composition, activities of metabolic enzymes, and expressions of energy homeostasis-related genes and six hifαs genes were measured. The results indicated that only the HC diet could significantly improve the resistance to hypoxia challenge. Moreover, the HC diet feeding caused higher glycogen deposition in the liver and muscle, and these glycogens were significantly reduced after 6-h acute hypoxia challenge. Meanwhile, the lactate content in the liver and blood was increased in the HC groups. At hypoxia status, the relative mRNA expressions of the genes related to glycolysis, ATP production, insulin signaling pathway, and hif-3a (hif1al) were all significantly increased in the muscle of the HC diet-fed fish. This study revealed that high-carbohydrate diet could improve the resistance to hypoxia by activating glycolysis and hif/insulin signaling pathway in zebrafish, mainly in the muscle, to efficiently supply energy. Therefore, our results highlight the importance of dietary carbohydrate in resisting hypoxia in fish.
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http://dx.doi.org/10.1007/s10695-019-00742-2DOI Listing
April 2020

Systematic comparative analysis of single-nucleotide variant detection methods from single-cell RNA sequencing data.

Genome Biol 2019 11 19;20(1):242. Epub 2019 Nov 19.

School of Life Sciences and BIOPIC, Peking University, Beijing, China.

Background: Systematic interrogation of single-nucleotide variants (SNVs) is one of the most promising approaches to delineate the cellular heterogeneity and phylogenetic relationships at the single-cell level. While SNV detection from abundant single-cell RNA sequencing (scRNA-seq) data is applicable and cost-effective in identifying expressed variants, inferring sub-clones, and deciphering genotype-phenotype linkages, there is a lack of computational methods specifically developed for SNV calling in scRNA-seq. Although variant callers for bulk RNA-seq have been sporadically used in scRNA-seq, the performances of different tools have not been assessed.

Results: Here, we perform a systematic comparison of seven tools including SAMtools, the GATK pipeline, CTAT, FreeBayes, MuTect2, Strelka2, and VarScan2, using both simulation and scRNA-seq datasets, and identify multiple elements influencing their performance. While the specificities are generally high, with sensitivities exceeding 90% for most tools when calling homozygous SNVs in high-confident coding regions with sufficient read depths, such sensitivities dramatically decrease when calling SNVs with low read depths, low variant allele frequencies, or in specific genomic contexts. SAMtools shows the highest sensitivity in most cases especially with low supporting reads, despite the relatively low specificity in introns or high-identity regions. Strelka2 shows consistently good performance when sufficient supporting reads are provided, while FreeBayes shows good performance in the cases of high variant allele frequencies.

Conclusions: We recommend SAMtools, Strelka2, FreeBayes, or CTAT, depending on the specific conditions of usage. Our study provides the first benchmarking to evaluate the performances of different SNV detection tools for scRNA-seq data.
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http://dx.doi.org/10.1186/s13059-019-1863-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862814PMC
November 2019

Sodium acetate alleviated high-carbohydrate induced intestinal inflammation by suppressing MAPK and NF-κB signaling pathways in Nile tilapia (Oreochromis niloticus).

Fish Shellfish Immunol 2020 Mar 12;98:758-765. Epub 2019 Nov 12.

Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), College of Life Sciences, East China Normal University, Shanghai, 200241, China. Electronic address:

With the development of aquaculture industry, high-carbohydrate diet is used to stimulate protein-sparing effect and reduce feed cost. However, fish utilize carbohydrates poorly in general, and instead, high level of carbohydrates in the diet influence the growth condition of fish. How to alleviate the side effects of high carbohydrate diet on fish health has attracted more and more attentions. In the present study, Nile tilapia (Oreochromis niloticus) were fed with 25% and 45% of carbohydrate diet for eight weeks. Higher body weight but lower resistance to pathogen was found in 45% carbohydrate diet group. Higher expression level of inflammation cytokines, increased expression of total NF-κB protein and phosphorylated NF-κB protein (p-NF-κB) were detected in higher carbohydrate group. Concentration of short-chain fatty acids (SCFAs) was measured and the results indicated that high-carbohydrate diet decreased acetate content in the intestine. In order to detect the relationship between the decreased concentration of acetate and lower resistance to pathogen in high-carbohydrate group, 45% of carbohydrate diets (HC) supplemented with different concentrations of sodium acetate (HC + LA, 100 mmol/L; HC + MA, 200 mmol/L; HC + HA, 400 mmol/L) were used to raise Nile Tilapia for eight weeks. The results indicated that addition of 200 mmol/L sodium acetate (HC + MA) reduced the mortality when fish were challenged with Aeromonas hydrophila. Furthermore, we also found that addition of 200 mmol/L sodium acetate mainly inhibited p38 mitogen-activated protein kinase (p38MAPK) and NF-κB phosphorylation to decrease the expression level of inflammation cytokines (IL-8, IL-12, TNF-α and IL-1β) in the intestine. The present study indicated that certain concentration of sodium acetate could alleviate high-carbohydrate induced intestinal inflammation mainly by suppressing MAPK activation and NF-κB phosphorylation.
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http://dx.doi.org/10.1016/j.fsi.2019.11.024DOI Listing
March 2020

The Responses of Germ-Free Zebrafish () to Varying Bacterial Concentrations, Colonization Time Points, and Exposure Duration.

Front Microbiol 2019 18;10:2156. Epub 2019 Sep 18.

Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai, China.

Colonizing germ-free (GF) zebrafish with specific bacterial species provides the possibility of understanding the influence on host biological processes including gene expression, development, immunity, and behavioral responses. It also enlightens our understanding on the host-microbe interactions within the physiological context of a living host. However, the responses of GF zebrafish to various colonization conditions such as bacterial concentrations, colonization time points, and exposure duration remain unclear. To address this issue, we explored the responses of GF zebrafish by using two bacterial species at varying concentrations, colonization time points and exposure duration. Therefore, we mono-associated GF zebrafish with DH5α or WB800N at concentrations ranging from 10 to 10 CFU/ml either at 3 day post fertilization (dpf) or 5 dpf for 24 or 48 h. We evaluated the responses of GF zebrafish by analyzing the survival rate, colonization efficiency, nutrients metabolism, intestinal cell proliferation, innate immunity, stress, and behavior responses by comparing it to conventionally raised zebrafish (CONR) and GF zebrafish. The results indicated that the final bacteria concentrations ranging from 10 to 10 CFU/ml did not cause any mortality when GF mono-associated larvae were exposed to either DH5α or WB800N at 3 or 5 dpf, while concentrations ranging from 10 to 10 CFU/ml increased the mortality, particularly for 5 dpf owing to the decrease in dissolved oxygen level. The DH5α mainly induced the expression of genes related to nutrients metabolism, cell proliferation and immunity, while WB800N mainly upregulated the expression of genes related to immunity and stress responses. Moreover, our data revealed that GF zebrafish showed higher levels of physical activity than CONR and the microbial colonization reduced the hyperactivity of GF zebrafish, suggesting colonization of bacteria affected behavior characteristics. This study provides useful information on bacterial colonization of GF zebrafish and the interaction between the host and microbiota.
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http://dx.doi.org/10.3389/fmicb.2019.02156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760068PMC
September 2019

Inhibition of intestinal lipases alleviates the adverse effects caused by high-fat diet in Nile tilapia.

Fish Physiol Biochem 2020 Feb 13;46(1):111-123. Epub 2019 Sep 13.

Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, 200241, People's Republic of China.

Intestinal lipases are fat-digesting enzymes, which play vital roles in lipid absorption in the intestine. To study the regulation of intestinal lipase activity in systemic lipid metabolism in fish, especially in the metabolic diseases caused by high-fat diet (HFD) feeding, we inhibited intestinal lipases in Nile tilapia to investigate the physiological consequences. In the present study, Nile tilapia were firstly fed with HFD (12% fat) for 6 weeks to establish a fatty fish model. Afterwards, Orlistat as a potent intestinal lipase inhibitor was added into the HFD for the following 5-week feeding trial, with two dietary doses (Orlistat16 group, 16 mg/kg body weight; Orlistat32 group, 32 mg/kg body weight). After the trial, both doses of Orlistat treatment significantly reduced intestinal lipase activity, fat absorption, hepatic lipid accumulation, and gene expression of lipogenesis, whereas increased gene expression of lipid catabolism. Moreover, intestinal lipase inhibition increased immune enzyme activities, antioxidant capacity, and gene expression of anti-inflammatory cytokines, whereas lowered gene expression of pro-inflammatory cytokines. Besides, Orlistat could also improve the structure of the intestine and increase expression of intestinal tight-coupling protein. Taken together, intestinal lipase inhibition alleviated the adverse effects caused by HFD in Nile tilapia. Thus, intestinal lipases played key roles in absorbing dietary lipid and could be a promising target in regulating systemic lipid metabolism in fish.
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http://dx.doi.org/10.1007/s10695-019-00701-xDOI Listing
February 2020

The effects of glycine-glutamine dipeptide replaced l-glutamine on bovine parthenogenetic and IVF embryo development.

Theriogenology 2020 Jan 6;141:82-90. Epub 2019 Sep 6.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, 712100, PR China; Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi, 712100, PR China. Electronic address:

Relative to alanine and serine amino acid levels, glutamine is highly abundant in follicular fluid, and is an important source of energy required for oocyte maturation and embryo development. Thus, glutamine is an essential component of in vitro embryo culture media. However, glutamine has poor stability and degrades spontaneously in solution to form ammonia and pyrrolidonecarboxylic acid. In the present study, we aimed to explore the effect of substituting l-glutamine with glycine-glutamine, a more stable glutamine, on development of early parthenogenetic embryos and in vitro fertilization (IVF) embryos in bovine. Results revealed that glycine-glutamine can significantly increase cleavage rate (parthenogenetic embryos:87.24% vs. 72.61%, IVF embryos:89.33% vs. 83.79%, P < 0.01), blastocyst number (parthenogenetic embryos:24.98% vs. 18.07%, IVF embryos:33.53% vs. 27.29%, P < 0.01), and blastocyst number (parthenogenetic embryos:96 vs. 76, IVF embryos:114 vs. 109, P < 0.01), reduce blastocyst apoptosis (parthenogenetic embryos:3.72% vs. 6.65%, IVF embryos:2.53% vs.6.23%, P < 0.01), alleviate embryo ammonia toxicity, and reduce the content of reactive oxygen species (ROS) compared with the l-glutamine. In addition, glycine-glutamine can alter epigenetic reprogramming by increasing the expression of HDAC1 (Histone Deacetylase 1) and decreasing the relative expression levels of H3K9 acetylation in early parthenogenetic embryos and IVF embryos. From our present study, we concluded that glycine-glutamine is an effective substitute of glutamine in modified synthetic oviduct fluid with amino acids (mSOFaa).
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http://dx.doi.org/10.1016/j.theriogenology.2019.09.005DOI Listing
January 2020

Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing piperazine as inhibitors of PI3Kα.

Bioorg Chem 2019 11 30;92:103238. Epub 2019 Aug 30.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address:

PI3K pathway has been heavily studied and is one of the most potential targets for various cancer treatment. Herein, we designed and synthesized a series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates contained piperazine based on our previous research. They were evaluated for their PI3Kα wild-type and H1047R mutant inhibitory activities and anticancer effects in vitro. Most of these compounds displayed the potential antiproliferative activities against four cancer cell lines (HCT-116, A549, Huh7 and HL60). Among them, Compound 4p revealed the remarkable antiproliferative activity and was selected for further biological evaluation. Compound 4p displayed the potent activity against both PI3Kα wild-type and H1047R mutant, and a certain degree of selectivity for PI3Kα over PI3Kβ, γ and δ, and meanwhile it can remarkable down-regulate the phosphorylation of Akt. In addition, compound 4p was found to induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. The above results suggested that compound 4p could be considered as a promising PI3Kα inhibitor.
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http://dx.doi.org/10.1016/j.bioorg.2019.103238DOI Listing
November 2019

Development of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates bearing sulfonylpiperazine as antitumor inhibitors targeting PI3Kα.

Eur J Med Chem 2019 Nov 18;182:111630. Epub 2019 Aug 18.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, PR China. Electronic address:

PI3K signal pathway plays a vital role in cellular functions and becomes an attractive approach for cancer therapy. Herein, a new series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivatives bearing sulfonylpiperazine based on the PI3K inhibitors and our previous research. They were screened for their PI3K inhibitory activities and anticancer effects in vitro. Biological studies indicated that compound 7m revealed the remarkable antiproliferative activity (IC ranging from 0.03 to 0.09 μM) against four cancer cell lines (A549, Huh7, HL60 and HCT-116). Besides, compound 7m displayed a certain selective for PI3Kα (IC = 0.009 μM) over PI3Kβ, γ and δ, and meanwhile, it can remarkable decreased the expression level of p-Akt (Ser473) and p-S6K. In addition, compound 7m could not only induce HCT-116 cell arrest at G1 phase in a dose-dependent manner, but also induce cell apoptosis via upregulation of Bax and cleaved-caspase 3/9, and downregulation of Bcl-2. Besides, compound 7m can remarkably inhibit the growth of tumor in vivo. The above results suggested that compound 7m could be considered as a promising PI3Kα inhibitor.
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http://dx.doi.org/10.1016/j.ejmech.2019.111630DOI Listing
November 2019

Inhibited autophagy impairs systemic nutrient metabolism in Nile tilapia.

Comp Biochem Physiol A Mol Integr Physiol 2019 10 4;236:110521. Epub 2019 Jul 4.

LANEH, School of Life Sciences, East China Normal University, Shanghai, China. Electronic address:

Autophagy is a conserved cellular degradation process through which intracellular components are degraded by the lysosome, but its roles in fish metabolism have not been studied in depth. Therefore, the present study aimed to investigate whether autophagy plays a key role in maintaining metabolic homeostasis in fish. In an 8-week feeding trial, Nile tilapia were fed either a control diet with medium fat and medium carbohydrate (Control), or a control diet supplemented with a classic autophagy inhibitor (chloroquine, CQ). CQ supplementation significantly inhibited autophagy and impaired fish growth and protein synthesis, and the glycolysis was stimulated, accompanied by fat accumulation, high oxidative stress and inflammation. Physiological status and gene expressions suggested that impaired autophagy might be at least one cause of the metabolic diseases which has been commonly seen in aquaculture. These results indicate that inhibition of autophagy could significantly affect the metabolism of lipid, carbohydrate and protein in fish; hence, autophagy could play important roles in maintaining homeostasis of nutrient metabolism in cultured fish.
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http://dx.doi.org/10.1016/j.cbpa.2019.06.021DOI Listing
October 2019

Dietary Aroclor 1254-Induced Toxicity on Antioxidant Capacity, Immunity and Energy Metabolism in Chinese Mitten Crab : Amelioration by Vitamin A.

Front Physiol 2019 12;10:722. Epub 2019 Jun 12.

Laboratory of Aquaculture Nutrition and Environmental Health, School of Life Sciences, East China Normal University, Shanghai, China.

Effects of dietary Polychlorinated biphenyl (PCB) exposure and dietary vitamin A supplementation on Chinese mitten crab were studied with the aim to explain dietary PCB toxicity and toxic alleviation by vitamin A intake in crab. Four diets were used including three experimental diets containing 0, 80000 or 240000 IU/kg vitamin A with each experimental diet containing 10 mg PCB/kg diet, and a control diet (without vitamin A and PCB supplementation) in 56 days feeding trial. Crabs fed the PCB-only diet had significantly lower weight gain than those fed the control diet. No significant difference was observed in crab survival among all groups. Crabs fed the PCB-only diet had a significantly higher malondialdehyde content and antioxidase superoxide dismutase activity in the serum and hepatopancreas, and higher erythromycin N-demethylase and glutathione S-transferase activities in the hepatopancreas than those fed the control diet. However, supplementation of dietary vitamin A decreased the levels of all these parameters. The hepatopancreatic cytochrome P450 2 and 4 (CYP2, CYP4), fatty acid binding proteins 3 and 10 (FABP3, FABP10) and intracellular lipolytic enzyme (IL) Messenger Ribonucleic Acid (mRNA) levels in the PCB-only group were significantly higher than those in the control group, and dietary 240000 IU/kg vitamin A supplementation decreased hepatopancreatic CYP4, FABP3, FABP10 and IL enzyme mRNA level. The crabs fed 80000 IU/kg vitamin A supplementation diet had the highest level of retinoid X receptor mRNA in the hepatopancreas. The structure of the hepatopancreas was damaged and the deposit of lipid droplets decreased with dietary PCB exposure. Both levels of vitamin A supplementation alleviated the damage and increased lipid droplets in the hepatopancreas. Dietary PCB exposure significantly reduced total hemocyte count (THC), and phenoloxidase, acid phosphatase activities in the serum. Post-challenge survival of crab in the experimental PCB-only diet group was low compared with that in the control. Supplementation of 240000 IU/kg vitamin A significantly increased the THC and phenoloxidase activity in the serum and post-challenge survival compared with those in the PCB-only group. This study indicates that dietary vitamin A can improve the antioxidant capacity, immune response, detoxification enzymes activities, energy metabolism and hepatopancreas tissue structure of Chinese mitten crab fed PCB contaminated diets.
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http://dx.doi.org/10.3389/fphys.2019.00722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581683PMC
June 2019

Sperm-borne small RNAs regulate α-tubulin acetylation and epigenetic modification of early bovine somatic cell nuclear transfer embryos.

Mol Hum Reprod 2019 08;25(8):471-482

Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.

Accumulated evidence indicates that sperm-borne small RNA plays a crucial role in embryonic development, especially the absence of the sperm-borne small RNA might be a major cause of the abnormal development of cloned embryos. In this study, we found that sperm-borne small RNA can affect abnormal pronuclear-like structures, postpone the timing of first embryo cleavage and enhance developmental competence of bovine somatic cell nuclear transfer (SCNT) embryos. In addition, the supplementation of sperm-borne small RNA can significantly increase live birth rates and decrease the birth weights of cloned offspring. To investigate the underlying mechanisms, the levels of α-tubulin K40 acetylation (Ac α-tubulin K40) and histone H3 lysine 9 trimethylation (H3K9me3) during early embryo development were investigated in SCNT embryos with sperm-borne small RNA supplementation (termed as T-NT), compared to those normal SCNT embryos and embryos obtained from standard IVF. The results showed that sperm-borne small RNA can significantly decrease the H3K9me3 levels at the pronuclear and two-cell stages, while significantly increase Ac α-tubulin K40 levels at anaphase and telophase of bovine SCNT embryos during the first cleavage. Collectively, our study for the first time demonstrates that sperm-borne small RNA plays a crucial role in the developmental competence of SCNT embryos by regulating H3K9me3 and Ac α-tubulin K40. Further studies will be required to determine how sperm small RNA regulate the H3K9me3 and Acα-tubulin K40. Our study suggests that the supplementation of sperm-borne small RNA is a potential application to improve the cloning efficiency.
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http://dx.doi.org/10.1093/molehr/gaz023DOI Listing
August 2019

Design, synthesis and biological evaluation of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates containing sulfonamido as potential PI3Kα inhibitors.

Bioorg Med Chem 2019 06 15;27(11):2261-2267. Epub 2019 Apr 15.

State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address:

A series of novel chromeno[4,3-c]pyrazol-4(2H)-one derivates contained sulfonamido were designed and synthesized, and their anticancer effects in vitro was evaluated to develop some new PI3Kα inhibitors. Most of desired compounds exhibited the better antiproliferative activities against four cancer cell lines than that of LY294002. Out of them, compound 4o displayed the potent antiproliferative activity and high selectivity against the PI3Kα protein and it can induce apoptosis of HCT116 in a dose-dependent manner. Western blot assay indicated that compound 4o obviously down-regulated expression of p-Akt (S473). Molecular docking was performed to clarify the possible binding mode between compound 4o and PI3Kα. All these results indicated that compound 4o could be a potential inhibitor of PI3Kα.
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http://dx.doi.org/10.1016/j.bmc.2019.04.021DOI Listing
June 2019

Dietary oils modify lipid molecules and nutritional value of fillet in Nile tilapia: A deep lipidomics analysis.

Food Chem 2019 Mar 3;277:515-523. Epub 2018 Nov 3.

LANEH, School of Life Sciences, East China Normal University, 200241 Shanghai, China. Electronic address:

The nutritional value of fish fillet can be largely affected by dietary oils. However, little is known about how dietary oils modify lipid molecules in fish fillets. Through biochemical and lipidomics assays, this study demonstrated the molecular characteristics of fillet lipids in Nile tilapia fed with different oils for six weeks. High 18:2n-6 and low 18:3n-3 deposition in phosphoglycerides resulted high 18:2n-6/18:3n-3 ratio in tilapia. Dietary n-3 VLCUFAs intake increased its deposition at sn-1/3 of triglycerides and at sn-2 of phosphatidylcholines. Irrespective of dietary oil, 16:0 was distributed preferentially at the outer positions of glycerol backbone. High 18:2n-6 accumulated at sn-2 position for fish fed with n-3 PUFA-enriched oils. High 18:3n-3 deposited at sn-1/3 in TG, sn-1 in phosphatidylethanolamines, while at sn-2 in phosphatidylcholines. Together, dietary oils change the composition and positional distribution of fatty acids on the glycerol backbone, and change nutritional value of fish for human health.
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http://dx.doi.org/10.1016/j.foodchem.2018.11.020DOI Listing
March 2019

Lineage tracking reveals dynamic relationships of T cells in colorectal cancer.

Nature 2018 12 29;564(7735):268-272. Epub 2018 Oct 29.

Beijing Advanced Innovation Centre for Genomics, Peking-Tsinghua Centre for Life Sciences, Peking University, Beijing, China.

T cells are key elements of cancer immunotherapy but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens, could serve as lineage tags to track these T cells in tumours. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8 effector and 'exhausted' T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8 effector memory cells, implicating a TCR-based fate decision. Of the CD4 T cells, most tumour-infiltrating T regulatory (T) cells showed clonal exclusivity, whereas certain T cell clones were developmentally linked to several T helper (T) cell clones. Notably, we identified two IFNG T1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors -the GZMK effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13BHLHE40 T1-like cell clusters, which were associated with BHLHE40. Only CXCL13BHLHE40 T1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13BHLHE40 T1-like cells and CD8 exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.
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http://dx.doi.org/10.1038/s41586-018-0694-xDOI Listing
December 2018