Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice.

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

Common pathogenic bacteria-induced reprogramming of the host proteinogenic amino acids metabolism.

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics.

A Comparative Study about the Neuroprotective Effects of DHA-Enriched Phosphatidylserine and EPA-Enriched Phosphatidylserine against Oxidative Damage in Primary Hippocampal Neurons.

Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.

Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life.

The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

N-3 PUFA Deficiency from Early Life to Adulthood Exacerbated Susceptibility to Reactive Oxygen Species-Induced Testicular Dysfunction in Adult Mice.

Homeostasis of reactive oxygen species is required to maintain sperm maturation and capacitation. Docosahexaenoic acid (DHA) is accumulated in testicles and spermatozoa and has the ability to manipulate the redox status. The effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) deficiency from early life to adulthood on the physiological and functional properties of males under the redox imbalance of testicular tissue deserve attention. The consecutive injection of hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) for 15 days to induce oxidative stress in testicular tissue was used to elucidate the consequences of testicular n-3 PUFA deficiency. The results indicated that reactive oxygen species treatment in adult male mice with DHA deficiency in the testis could reduce spermatogenesis and disrupt sex hormone production, as well as trigger testicular lipid peroxidation and tissue damage. N-3 PUFA deficiency from early life to adulthood resulted in higher susceptibility to testicular dysfunction in the germinal function of supplying germ cells and the endocrine role of secreting hormones through the mechanism of aggravating mitochondria-mediated apoptosis and destruction of blood testicular barrier under oxidative stress, which might provide a basis for humans to reduce susceptibility to chronic disease and maintain reproductive health in adulthood through dietary interventions of n-3 PUFAs.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

Eicosapentaenoic acid-enriched phospholipids alleviate glucose and lipid metabolism in spontaneously hypertensive rats with CD36 mutation: a precise nutrition strategy.

Previous studies have found that eicosapentaenoic acid-enriched phospholipids (EPA-PLs) alleviated glucose and lipid metabolism, which was accompanied by an increase of cluster of differentiation 36 (CD36). However, the effects of EPA-PLs on glucose and lipid metabolism in the case of CD36 mutation are unclear. Thus, spontaneously hypertensive rats/NCrl (SHR) were used as a CD36 mutation model to determine the effects of dietary 2% EPA-PLs for 4 weeks on glucose and lipid metabolism. The results showed that the intervention of EPA-PLs significantly alleviated the abnormal increase of serum free fatty acid levels and glycerol levels in SHRs. Moreover, the administration of EPA-PLs decreased the triglyceride levels and cholesterol levels by 31.1% and 37.9%, respectively, in the liver. Dietary EPA-PLs had no effect on epididymal fat weight, but EPA-PLs inhibited adipocyte hypertrophy in SHRs. Further mechanistic research found that EPA-PL pretreatment significantly reduced triacylglycerol catabolism and increased fatty acid ß-oxidation. Additionally, the administration of EPA-PLs decreased the area under the curve of the intraperitoneal glucose tolerance test and fasting serum insulin levels by activating the IRS/PI3K/AKT signaling pathway. Furthermore, EPA-PL pretreatment significantly increased the CD36 gene expression in the liver tissues, adipose tissues and muscle tissues even in the case of CD36 mutation. These results indicated that EPA-PLs alleviate glucose and lipid metabolism in the case of CD36 mutation, which provides a precise nutrition strategy for people with CD36 mutation.

N-3 PUFA Deficiency Aggravates Streptozotocin-Induced Pancreatic Injury in Mice but Dietary Supplementation with DHA/EPA Protects the Pancreas via Suppressing Inflammation, Oxidative Stress and Apoptosis.

It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional ß-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA ß-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA ß-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet ß-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.

Free astaxanthin-rich diets enhanced astaxanthin accumulation in egg yolks compared to esterified astaxanthin-rich diets.

As an oxycarotenoid with strong antioxidant properties, astaxanthin can considerably boost pigmentation and improve the nutritional value of eggs. The purpose of this study was to elucidate the comparative effects of different chemical structures of astaxanthin including free astaxanthin, monoester-enriched astaxanthin and diester-enriched astaxanthin on the nutritional enhancement of eggs within 20 days. The results showed that supplementation of free astaxanthin to laying hens was more effective in accumulating astaxanthin in egg yolks than supplementation with esterified astaxanthin. The retention rate of free astaxanthin was approximately 12.0 % at the plateau phase in egg yolk, while that of monoester-enriched and diester-enriched astaxanthin were 4.0 % and 2.5 %, respectively. Free astaxanthin possessed a high retention rate and pigmentation effect compared with esterified astaxanthin, which might provide a basis for astaxanthin enhancement in eggs and potential application in nutritional functional foods.

The synergistic effect of sea cucumber saponins and caffeine on preventing obesity in high-fat diet-fed mice by extending the action duration of caffeine.

BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.

A Comparative Study of the Anti-Obesity Effects of Dietary Sea Cucumber Saponins and Energy Restriction in Response to Weight Loss and Weight Regain in Mice.

Dietary supplementation of sea cucumber saponins and calorie restriction have been proved to be effective in alleviating obesity, but the differences of anti-obesity effects between sea cucumber saponins and energy restriction during weight loss and weight regain are still unknown. In the present study, high-fat-induced obesity mice were randomly divided into three groups, including a high-fat diet group (HF), an energy restriction by 40% group (HF-L), and a sea cucumber saponins group (HF-S), to compare the effects of dietary sea cucumber saponins and energy restriction on the weight, glucose, and lipid metabolism of obese mice during weight loss and weight regain. The results showed that dietary 0.06% sea cucumber saponins and limiting energy intake by 40% had the same weight loss effect. Interestingly, sea cucumber saponins could alleviate impaired glucose tolerance and insulin resistance caused by obesity. In addition, the inhibited SREBP-1c mediated lipogenesis might lead to the alleviation of weight regain after resuming the high-fat diet even when sea cucumber saponins were no longer supplemented. In contrast, limiting energy intake tended to promote lipid synthesis in the liver and white adipose tissue after restoring a high-fat diet, and inflammation was also induced. The findings indicated that sea cucumber saponins could replace calorie restriction to prevent obesity and might be used as a functional food or drug to resist obesity and related diseases caused by obesity.

Antarctic krill oil exhibited synergistic effects with nobiletin and theanine in ameliorating memory and cognitive deficiency in SAMP8 mice: Applying the perspective of the sea-land combination to retard brain aging.

The complex pathogenesis of Alzheimer's disease (AD) leads to a limited therapeutic effect; therefore, the combination of multiple bioactive ingredients may be more effective in improving AD due to synergistic effects. Based on the perspective of the sea-land combination, the effects of sea-derived Antarctic krill oil (AKO) combined with land-derived nobiletin (Nob) and L-theanine (The) on memory loss and cognitive deficiency were studied in senescence-accelerated prone 8 mice (SAMP8). The results demonstrated that AKO combined with The significantly increased the number of platform crossings in the Morris water maze test by 1.6-fold, and AKO combined with Nob significantly increased the preference index in a novel object recognition test. AKO exhibited synergistic effects with Nob and The in ameliorating recognition memory and spatial memory deficiency in SAMP8 mice, respectively. Further research of the mechanism indicated that AKO exhibited synergistic effects with Nob in suppressing ß-amyloid (Aß) aggregation, neurofibrillary tangles, and apoptosis and neuroinflammation, while the synergistic effects of AKO and The involved in synaptic plasticity and anti-neuroinflammation, which revealed that the combination was complex, not a mechanical addition. These findings revealed that the sea-land combination may be an effective strategy to treat and alleviate AD.

[Expression and significance of Treg/Th17 and CD4+/CD8+ T lymphocytes in experimental periodontitis in rats].

PURPOSE: To explore the expression of helper T cell 17/regulatory T cell (Th17/Treg) and CD4+/CD8+ T lymphocyte in experimental periodontitis in rats, and analyze its clinical significance. METHODS: Twenty SPF male SD rats were randomly divided into experimental group (inoculate Porphyromonas gingivalis suspension into gingival sulcus) and control group, with 10 rats in each group. The experimental group was smeared with Porphyromonas gingivalis suspension every other day within 1 week after operation, and the two groups were caged for 8 weeks. After the rats were sacrifical under anesthesia, the jaw tissue of the left maxillary second molar was stained with methylene blue to observe and measure the loss of alveolar bone (ABL). Hematoxylin-eosin (H-E) staining was used to observe the histopathological changes of the jaw. Rat peripheral blood mononuclear cells (PBMC) and T cells were isolated and cultured, Treg, Th17 cells and CD4+, CD8+ T lymphocytes in peripheral blood were detected by flow cytometry. The levels of serum interleukin-17(IL-17), IL-10 and IL-4, INF-γ were detected by enzyme-linked immunosorbent assay (ELISA). Expression changes of retinoic acid related orphan nuclear receptor (RORγt), forkhead wing like transcription factor 3 (Foxp3) and gap junction protein(Cx40) in jaw tissue were detected by Western blot. The data were statistically analyzed by SPSS 19.0 software package. RESULTS: Compared with the control group, ABL, peripheral blood Th17 ratio, Th17/Treg ratio, CD4+ ratio, CD4+/CD8+ T lymphocyte ratio, serum IL-17, IL-10 and IL-4 level, Foxp3 and Cx40 protein in jaw tissue were signifinantly increased in the experimental group(P<0.05), while Treg ratio, INF-γ, RORγt protein in jaw tissue significantly decreased(P<0.05) in the experimental group. CONCLUSIONS: Imbalance of Treg/Th17 and CD4+/CD8+ T lymphocytes leads to the abnormal high expression of inflammatory factors IL-17, IL-10 and IL-4, which may be closely related to the pathogenesis of experimental periodontitis.

Analysis of Antidepressant Activity of Huang-Lian Jie-Du Decoction Through Network Pharmacology and Metabolomics.

Depressive disorder is a common mental disorder characterized by depressed mood and loss of interest or pleasure. As the Herbal medicines are mainly used as complementary and alternative therapy for depression. This study aimed at exploring antidepressant activity of Huang-lian Jie-du Decoction (HLJDD), and evaluating active components and potential depression-associated targets. HLJDD was administered on chronic unpredictable mild stress-induced (CUMS) depressive mice. Behavior evaluation was performed through force swimming test (FST), novelty-suppressed feeding test (NSF), and open field test (OFT). Active components of HLJDD, potential targets, and metabolic pathways involved in depression were explored through systemic biology-based network pharmacology assay, molecular docking and metabonomics. FST assay showed that CUMS mice administered with HLJDD had significantly shorter immobility time compared with control mice. Further, HLJDD alleviated feeding latency of CUMS mice in NSFand increased moving distance and duration in OFT. In the following network pharmacology assay, thirty-eight active compounds in HLJDD were identified based on drug-like characteristics, and pharmacokinetics and pharmacodynamics profiles. Moreover, forty-eight molecular targets and ten biochemical pathways were uncovered through molecular docking and metabonomics. GRIN2B, DRD, PRKCA, HTR, MAOA, SLC6A4, GRIN2A, and CACNA1A are implicated in inhibition of depressive symptoms through modulating tryptophan metabolism, serotonergic and dopaminergic synaptic activities, cAMP signaling pathway, and calcium signaling pathway. Further network pharmacology-based analysis showed a correlation between HLJDD and tryptophan metabolism. A total of thirty-seven active compounds, seventy-six targets, and sixteen biochemical pathways were involved in tryptophan metabolism. These findings show that HLJDD acts on potential targets such as SLC6A4, HTR, INS, MAO, CAT, and FoxO, PI3K/Akt, calcium, HIF-1, and mTOR signaling pathways, and modulates serotoninergic and dopaminergic synaptic functions. In addition, metabonomics showed that tryptophan metabolism is the primary target for HLJDD in CUMS mice. The findings of the study show that HLJDD exhibited antidepressant effects. SLC6A4 and MAOA in tryptophan metabolism were modulated by berberine, baicalein, tetrahydroberberine, candicine and may be the main antidepressant targets for HLJDD.

Prevalence of Haemophilus parasuis"Glaesserella parasuis" in pigs in China: A systematic review and meta-analysis.

Haemophilus parasuis, a gram-negative bacterium as an early commensal colonizer in the upper respiratory tract of weaning pigs (Sus scrofa), is one of the most important bacterial pathogens affecting pig populations. It is the causative agent of Glässer's disease, causing systemic infection and polyserositis, meningitis, and arthritis. H. parasuis infection can result in high mortality and morbidity with, the significant economic losses for pig producers. To estimate the overall disease prevalence of H. parasuis in pigs from China, we performed a meta-analysis using five bibliographical databases: PubMed, ScienceDirect, CNKI, Wanfang, and VIP Chinese Journal Databases. A total of 41 articles published between 2005 and 2019, fulfilled the final inclusion criteria. The overall prevalence of H. parasuis in pigs in China was 27.8 % with the highest prevalence between 2011 and 2015 (41.0 %). In terms of pig age, the point estimate of H. parasuis prevalence was higher in suckling piglets (29.2 %) compared with that for other pig ages. The prevalence in the serum subgroup (29.8 %) was higher than that in the nasal swab subgroup (12.5 %). The results of the present meta-analysis showed that H. parasuis infection was common in pig populations in China; therefore, effective control measures are necessary to reduce this threat to pig populations.

Expression profiles of circular RNAs in sheep skeletal muscle.

OBJECTIVE: Circular RNAs (circRNAs) are a newfound class of non-coding RNA in animals and plants. Recent studies have revealed that circRNAs play important roles in cell proliferation, differentiation, autophagy and apoptosis during development. However, there are few reports about muscle development-related circRNAs in livestock. METHODS: RNA sequencing analysis was employed to identify and annotate circRNAs from longissimus dorsi of sheep. Reverse transcription followed by real-time quantitative (q) polymerase chain reaction (PCR) analysis verified the presence of these circRNAs. Targetscan7.0 and miRanda were used to analyse the interaction of circRNA-microRNA (miRNA). To investigate the function of circRNAs, an experiment was conducted to perform enrichment analysis hosting genes of circRNAs using gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. RESULTS: About 75.5 million sequences were obtained from RNA libraries of sheep skeletal muscle. These sequences were mapped to 729 genes in the sheep reference genome. We identified 886 circRNAs, including numerous circular intronic RNAs and exonic circRNAs. Reverse transcription PCR (RT-PCR) and DNA sequencing analysis confirmed the presence of several circRNAs. Real-Time RT-PCR analysis exhibited resistance of sheep circRNAs to RNase R digestion. We found that many circRNAs interacted with muscle-specific miRNAs involved in growth and development of muscle, especially circ776. The GO and KEGG enrichment analysis showed that hosting genes of circRNAs was involved in muscle cell development and signaling pathway. CONCLUSION: The study provides comprehensive expression profiles of circRNAs in sheep skeletal muscle. Our study offers a large number of circRNAs to facilitate a better understanding of their roles in muscle growth. Meanwhile, we suggested that circ776 could be analyzed in future study.

miR-124/MCP-1 signaling pathway modulates the protective effect of itraconazole on acute kidney injury in a mouse model of disseminated candidiasis.

Previous studies have indicated that monocyte chemoattractant protein-1 (MCP­1), also referred to as C­C motif chemokine ligand 2, has a significant role in the pathogenesis of sepsis, however, how microRNAs (miRs) contribute to this process remains to be fully elucidated. In the present study, using a mouse model of disseminated candidiasis, the renoprotective effect of itraconazole (ITR) and adenovirus­delivered miR­124 was investigated. The mice were treated with ITR (50 mg/kg) or transfected with miR­124 mimics via tail­vein injection 7 days prior to Candida albicans infection. The survival outcome was monitored following candidiasis­induced sepsis with ITR or miR­124 mimics treatment. The levels of pro­inflammatory cytokines, including tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß) and IL­6, were determined using enzyme­linked immunosorbent assays. The mRNA and protein levels were assayed using reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively. The results showed that ITR and miR­124 mimics improved the survival outcome in candidiasis­induced septic mice. The findings also indicated a significant downregulation in the serum levels of TNF­α, IL­1ß and IL­6 in the septic mice treated with ITR or miR­124 mimics. Of note, ITR treatment significantly increased the expression of miR­124 and decreased the levels of MCP­1 in the kidneys of the septic mice. It was also shown that the overexpression of miR­124 reduced the expression of MCP­1 and attenuated candidiasis­induced acute kidney injury (AKI) in septic mice. Transfection with miR­124 mimics was equivalent to ITR in reducing the excessive inflammatory response and renal lesions in septic mice. These results provided evidence supporting the use of miR­124 mimics as a therapeutic approach for attenuating candidiasis-induced AKI.

Transformation of dissolved organic matter in concentrated leachate from nanofiltration during ozone-based oxidation processes (O3, O3/H2O2 and O3/UV).

In this study, the transformation of dissolved organic matter (DOM) in nanofiltration concentrated leachate during three ozone-based oxidation processes (i.e., O3, O3/H2O2 and O3/UV) was investigated. The transformation characteristics of DOM were evaluated by gel filtration chromatography (GFC), XAD-8 resin fractionation, excitation-emission matrix fluorescence spectroscopy (EEM) and Fourier transform infrared spectroscopy (FTIR). Compared with O3-alone process, the removal efficiencies of COD, TOC, and color were improved in O3-combined processes (i.e., O3/H2O2 and O3/UV) approximately by 10-15%, 7-15%, and 15-20%, respectively. Humic acid (HA) was completely degraded and preferentially reacted with the oxidants during ozonation processes. HA was first converted into fulvic acid (FA), and then the majority of these intermediates were further converted to hydrophilic fraction (HyI). The GFC results indicated that the broader molecular weight distribution of DOM was observed, and high molecular weight DOM (i.e., 0.45 µm-100 kDa) was successfully converted to low molecular weight organics in the range of 1-10 kDa after ozonation reactions. The EEM spectra also showed that HA and FA were effectively converted into HyI after ozonation for 90 min. It is suggested that ozone-based oxidation processes could effectively change the DOM distribution and fluorescence features of concentrated leachate.

[Effects of pH and Complexing Agents on Sb(â ¤) Adsorption onto Birnessite and Ferrihydrite Surface].

Effects of pH and complexing agents on Sb (Ⅴ) adsorption onto birnessite and ferrihydrite surface were investigated.The results indicated that birnessite and ferrihydrite had strong ability to adsorb Sb (Ⅴ).The removal efficiencies of Sb (Ⅴ) by birnessite and ferrihydrite were dependent on the initial pH in solution.The removal efficiency of Sb (Ⅴ) increased with the decrease of solution pH.At pH 5.0,the removal efficiencies,adsorption rate and adsorption capacity were better than those at pH 7.0 or 9.0.The adsorption process of Sb (Ⅴ) on birnessite and ferrihydrite could be well described by the pseudo-second-order model.The Langmuir model best described the adsorption behavior of Sb (Ⅴ) by birnessite and ferrihydrite at pH 5.0.The presence of citric acid or EDTA had significant effect on Sb (Ⅴ) adsorption onto birnessite and ferrihydrite.