Enhancement of autophagy can alleviate oxidative stress, inflammation, and apoptosis induced by ammonia stress in yellow catfish Pelteobagrus fulvidraco.

Ammonia in aquatic environments is toxic to fish, directly impacting their growth performance and development. Activation of autophagy can facilitate intracellular component renewal and enhance an organism's adaptability to adverse environments. Therefore, this study investigates the impact of autophagy on the yellow catfish under acute ammonia stress. In this study, the yellow catfish intraperitoneally injected with 0.9 % sodium chloride were placed with 0 (CON group) and 125 (HA group) mg/L T-AN (Total ammonia nitrogen) dechlorinated water. The yellow catfish intraperitoneally injected with 30 mg/kg fish CQ (Chloroquine, HA + CQ group) and 1.5 mg/kg fish RAPA (rapamycin, HA + RAPA group) were placed in dechlorinated water containing 125 mg/L T-AN. The results showed that activation of autophagy by injecting with RAPA can alleviate oxidative stress (catalase, superoxide dismutase, total antioxidant capacity significantly increased, H2O2 content significantly decreased), and inflammatory response (pro-inflammatory factors TNF-α, MyD88, IL 1-ß gene expression decreased significantly), apoptosis (baxa, Bcl2, Tgf-ß, Smad2, Caspase3, Caspase 9 gene expression decreased significantly) induced by ammonia stress. In addition, activation of autophagy in yellow catfish can enhance ammonia detoxification by promoting the urea cycle and synthesis of glutamine (the mRNA level of CPS Ⅰ, ARG, OTC, ASS, ASL, and GS increased in the HA + RAPA group). The data above demonstrates that activating autophagy can alleviate oxidative stress, inflammatory responses, and cell apoptosis induced by ammonia stress. Therefore, enhancing autophagy is proposed as a potential strategy to mitigate the detrimental impacts of ammonia stress on yellow catfish.

Proteomic Analysis of Collagen: a Mass Spectrometry Approach to Material Identification of Shadow Puppet Cultural Relics.

Shadow puppets are a popular art form in various regions, including China, Indonesia, and Turkey, and are rich in cultural significance. However, there is a considerable lack of research on the materials, diseases and conservation techniques related to shadow puppet relics. Material identification is the basis for understanding the production process of ancient shadow puppet relics and evaluating their deterioration degree. The microscopic morphology and infrared spectroscopy results in our experiments showed that the traditional methods of ancient skin identification were not effective in the shadow puppet samples. In order to achieve accurate identification, we used biological mass-spectrometry in proteomics to examine two puppet relics and commercially available modern shadow puppets. The results showed that the above samples could be detected by mass spectrometry with abundant peptides, including peptides specific for bovine skin. These peptides cannot be found in other commonly used materials for making shadow puppets, including the skins of pig, sheep, deer and horse. It is worth mentioning that we have found the peptides specific to yellow cowhide in two ancient shadow puppet relics samples. Therefore, the proteomic evidence shows that the raw materials of the two shadow puppet relics samples are yellow cowhide. Four modern samples also confirmed the reliability of material identification using proteomics. The proteomic evidence shows that the biological mass spectrometry will contribute to the scientific research of shadow puppet relics and other skin and leather cultural relics.

Toxicity of common biocides used in aquaculture to embryos and larvae of Brachymystax tsinlingensis Li.

Brachymystax tsinlingensis Li is a threatened fish species endemic to China. With the problems of environmental factors and seeding breeding diseases, it is important to further improve the efficiency of seeding breeding and the basis of resource protection. This study investigated the acute toxicity of copper, zinc and methylene blue (MB) on hatching, survival, morphology, heart rate (HR) and stress behaviour of B. tsinlingensis. Eggs (diameter: 3.86 ± 0.07 mm, weight: 0.032 ± 0.004 g) of B. tsinlingensis were selected randomly from artificial propagation and developed from eye-pigmentation-stage embryos to yolk-sac stage larvae (length: 12.40 ± 0.02 mm, weight: 0.03 ± 0.001 g) and exposed to different concentrations of Cu, Zn and MB for 144 h in a series of semi-static toxicity tests. The acute toxicity tests indicated that the 96-h median lethal concentration (LC50 ) values of the embryos and larvae were 1.71 and 0.22 mg l-1 for copper and 2.57 and 2.72 mg l-1 for zinc, respectively, whereas the MB LC50 after 144-h exposure for embryos and larvae were 67.88 and 17.81 mg l-1 , respectively. The safe concentrations of copper, zinc and MB were 0.17, 0.77 and 6.79 mg l-1 for embryos and 0.03, 0.03 and 1.78 mg l-1 for larvae, respectively. Copper, zinc and MB treatments with concentrations greater than 1.60, 2.00 and 60.00 mg l-1 , respectively, led to a significantly low hatching rate and significantly high embryo mortality (P < 0.05), and copper and MB treatments with concentrations greater than 0.2 and 20 mg l-1 led to significantly high larvae mortality (P < 0.05). Exposure to copper, zinc and MB resulted in developmental defects, including spinal curvature, tail deformity, vascular system anomalies and discolouration. Moreover, copper exposure significantly reduced the HR of larvae (P < 0.05). The embryos exhibited an obvious change in behaviour, converting from the normal behaviour of emerging from the membrane head first to emerging tail first, with probabilities of 34.82%, 14.81% and 49.07% under copper, zinc and MB treatments, respectively. The results demonstrated that the sensitivity of yolk-sac larvae to copper and MB was significantly higher than that of embryos (P < 0.05) and that B. tsinlingensis embryos or larvae might be more resistant to copper, zinc and MB than other members of the Salmonidae family, which benefits their resource protection and restoration.

The SLC38A9-mTOR axis is involved in autophagy in the juvenile yellow catfish (Pelteobagrus fulvidraco) under ammonia stress.

The primary objective of this study was to examine the effect of acute ammonia stress on hepatic physiological alterations in yellow catfish by performing a comprehensive analysis of the metabolome and transcriptome. The present study showed that ammonia stress led to liver metabolic disruption, functional incapacitation, and oxidative damage. Transcriptomic and metabolomic analyses revealed transcriptional and metabolic differences in the liver of yellow catfish under control and high ammonia stress conditions. After 96 h of acute exposure to ammonia, the mRNA levels of 596 liver genes were upregulated, whereas those of 603 genes were downregulated. Enrichment analysis of the differentially expressed genes identified multiple signalling pathways associated with autophagy, including the endocytosis, autophagy-animal, and mammalian target of rapamycin signalling pathways. A total of 186 upregulated and 117 downregulated metabolites, primarily associated with amino acid biosynthesis pathways, were identified. Multi-omics integration revealed the solute carrier family 38 member 9 (SLC38A9)-mammalian target of rapamycin axis as a signalling nexus for amino acid-mediated modulation of autophagy flux, and q-PCR was used to assess the expression of autophagy-related genes (LC3a and sqstm1), revealing an initial inhibition followed by the restoration of autophagic flux during ammonia stress. Subsequent utilisation of arginine as a specific SLC38A9 activator during ammonia stress demonstrated that augmented SLC38A9 expression hindered autophagy, exacerbated ammonia toxicity, and caused a physiological decline (total cholesterol, total triglyceride, acid phosphatase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels were significantly increased), oxidative stress, and apoptosis. Autophagy activation may be an adaptive mechanism to resist ammonia stress.

Relationship between Parkinson's disease and cardio-cerebrovascular diseases: a Mendelian randomized study.

Parkinson's disease (PD) and cardio-cerebrovascular diseases are related, according to earlier studies, but these studies have some controversy. Our aim was to assess the impact of PD on cardiocerebrovascular diseases using a Mendelian randomization (MR) method. The data for PD were single nucleotide polymorphisms (SNPs) from a publicly available genome-wide association study (GWAS) dataset containing data on 482,730 individuals. And the outcome SNPs data is were derived from five different GWAS datasets. The basic method for MR analysis was the inverse variance weighted (IVW) approach. We use the weighted median method and the MR-Egger method to supplement the MR analysis conclusion. Finally, We used Cochran's Q test to test heterogeneity, MR-PRESSO method and leave-one-out analysis method to perform sensitivity analysis. We used ratio ratios (OR) to assess the strength of the association between exposure and outcome, and 95% confidence intervals (CI) to show the reliability of the results. Our findings imply that PD is linked to a higher occurrence of coronary artery disease (CAD) (OR = 1.055, 95% CI 1.020-1.091, P = 0.001), stroke (OR = 1.039, 95% CI 1.007-1.072, P = 0.014). IVW analyses for stroke's subgroups of ischemic stroke (IS) and 95% CI 1.007-1.072, P = 0.014). IVW analyses for stroke's subgroups of ischemic stroke (IS) and cardioembolic stroke (CES) also yielded positive results, respectively (OR = 1.043, 95% CI 1.008-1.079, P = 0.013), (OR = 1.076, 95% CI 1.008-1.149, P = 0.026). There is no evidence of a relationship between PD and other cardio-cerebrovascular diseases. Additionally, sensitivity analysis revealed reliable outcomes. Our MR study analysis that PD is related with an elevated risk of CAD, stroke, IS, and CES.

Causal influence of muscle weakness on cardiometabolic diseases and osteoporosis.

The causal roles of muscle weakness in cardiometabolic diseases and osteoporosis remain elusive. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of muscle weakness in the risk of cardiometabolic diseases and osteoporosis. 15 single nucleotide polymorphisms (SNPs, P < 5 × 10-8) associated with muscle weakness were used as instrumental variables. Genetic predisposition to muscle weakness led to increased risk of coronary artery disease (inverse variance weighted [IVW] analysis, beta-estimate: 0.095, 95% confidence interval [CI]: 0.023 to 0.166, standard error [SE]:0.036, P-value = 0.009) and reduced risk of heart failure (weight median analysis, beta-estimate: - 0.137, 95% CI - 0.264 to - 0.009, SE:0.065, P-value = 0.036). In addition, muscle weakness may reduce the estimated bone mineral density (eBMD, weight median analysis, beta-estimate: - 0.059, 95% CI - 0.110 to - 0.008, SE:0.026, P-value = 0.023). We found no MR associations between muscle weakness and atrial fibrillation, type 2 diabetes or fracture. This study provides robust evidence that muscle weakness is causally associated with the incidence of coronary artery disease and heart failure, which may provide new insight to prevent and treat these two cardiometabolic diseases.

Effects of ammonia and roxithromycin exposure on skin mucus microbiota composition and immune response of juvenile yellow catfish Pelteobagrus fulvidraco.

As an inevitable factor in aquaculture, ammonia plays a critical role in macrolide antibiotic resistance, leading to accumulating of antibiotic-resistant bacteria in fish skin mucus. In this study, four experimental groups were implemented to test the effects of ammonia alone or in combination with roxithromycin for 28 days on skin mucus microbial composition and the immune response of yellow catfish: CON (control), AN (50.00 mg L-1 total ammonia nitrogen, TA-N), ROX (100 µg L-1 roxithromycin), and HR (50.00 mg L-1 TA-N, 100 µg L-1 ROX). This study demonstrated that ammonia or roxithromycin exposure resulted in increased plasma ammonia content and decreased total antioxidant capacity. Compared with AN group, the combined exposure of ammonia and roxithromycin inhibited the skin mucus immune response. Microbial composition analysis showed that combined exposure of ammonia and roxithromycin had no significant effect on skin mucus α-diversity as compared with CON group. The abundance of Cetobacterium, Rhizobiales_Incertae_Sedis_uncultured and Acinetobacter was increased significantly with the combined effect of ammonia and roxithromycin, these bacteria may be potentially antibiotic-resistant. As compared with CON group, the combined exposure of ammonia and roxithromycin did not affect skin goblet cell counts. This study suggests that combined exposure to ammonia and ROX increases the risk of the emergence of antibiotic-resistant bacteria.

Temporal correlations of ferroptosis, inflammation and oxidative stress under acute ammonia exposure in brain tissue of yellow catfish (Pelteobagrus fulvidraco).

Ammonia is one of the most serious environmental stressors which severely affect fishery production. Ammonia toxicity to fish has a tight relationship with oxidative stress, inflammation and ferroptosis (a type of programmed cell death characterized by iron-dependent lipid peroxidation), but the temporal response of the above three in brain remains unclear. In the present study, yellow catfish were exposed to three concentrations of ammonia: low concentration (TA-N ˂ 0.01 mg L-1, LA), middle concentration (TA-N 5.70 mg L-1, MA), high concentration (TA-N 28.50 mg L-1, HA) for 96 h. Brain was selected as target tissues for analysis. Results showed that ammonia stress resulted in firstly increased contents of hydroxyl radical at 1 h, total iron at 12 h, malondialdehyde at 48 h, respectively, and decreased contents of GSH at 3 h. The initial high expression levels of ferroptosis (GPX4, system xc-, TFR1) and inflammatory-related factors (NF-ƙB p65, TNF, COX-2, and LOX-15B), antioxidant enzymes genes (SOD and CAT) were observed at first hour upon MA or HA stress. Combining all, it suggested that brain ferroptosis and inflammation were the first to be activated at the initial stage of ammonia stress, and then that provoked oxidative stress.

Comprehensive analysis of metabolomics on flesh quality of yellow catfish (Pelteobagrus fulvidraco) fed plant-based protein diet.

Background: To investigate the mechanism of plant protein components on nutritional value, growth performance, flesh quality, flavor, and proliferation of myocytes of yellow catfish (Pelteobagrus fulvidraco). Methods: A total of 540 yellow catfish were randomly allotted into six experimental groups with three replicates and fed six different diets for 8 weeks. Results and Conclusions: The replacement of fish meal with cottonseed meal (CM), sesame meal (SEM), and corn gluten meal (CGM) in the diet significantly reduced growth performance, crude protein, and crude lipid, but the flesh texture (hardness and chewiness) was observably increased. Moreover, the flavor-related amino acid (glutamic acid, glycine, and proline) contents in the CM, SEM, and CGM groups of yellow catfish muscle were significantly increased compared with the fish meal group. The results of metabolomics showed that soybean meal (SBM), peanut meal (PM), CM, SEM, and CGM mainly regulated muscle protein biosynthesis by the variations in the content of vitamin B6, proline, glutamic acid, phenylalanine, and tyrosine in muscle, respectively. In addition, Pearson correlation analysis suggested that the increased glutamic acid content and the decreased tyrosine content were significantly correlated with the inhibition of myocyte proliferation genes. This study provides necessary insights into the mechanism of plant proteins on the dynamic changes of muscle protein, flesh quality, and myocyte proliferation in yellow catfish.

Size dependent effects of nanoplastics and microplastics on the nitrogen cycle of microbial flocs.

NANO: and microplastics (NPs/MPs) are a new type of persistent environmental pollutant. Microbial flocs are a type of microbial aggregate commonly used in aquaculture. To investigate the impact of NPs/MPs on microbial flocs with different particle sizes: NPs/MPs-80 nm (M 0.08), NPs/MPs-800 nm (M 0.8), and NPs/MPs-8 µm (M 8), NPs/MPs exposure tests (28 days) and ammonia nitrogen conversion tests (24 h) were conducted. The results showed that the particle size was significantly higher in the M 0.08 group when compared with the control group (C group). The TAN (total ammonia nitrogen) content of each group maintained the order of M 0.08 > M 0.8 > M 8 > C from days 12-20. The nitrite content in the M 0.08 group was significantly higher on day 28 than that in the other groups. In the ammonia nitrogen conversion test, the nitrite content of the C group was significantly lower than that of the NPs/MPs exposure groups. The results suggested that NPs contributed to microbial aggregation and affected microbial colonization. In addition, NPs/MPs exposure could reduce microbial nitrogen cycling capacity, with a size-dependent toxicity difference of NPs > MPs. The findings of this study are expected to fill the research gap on the mechanisms of NPs/MPs' impact on microorganisms and the nitrogen cycle in aquatic ecosystems.

Responses of Micropterus salmoides under Ammonia Stress and the Effects of a Potential Ammonia Antidote.

Ammonia is a common environmental limiting factor in aquaculture. To investigate the effects of ammonia stress and explore the protective effect of N-carbamylglutamate (NCG) on Micropterus salmoides (M. salmoides), tissue sections and parameters related to oxidative stress and the inflammatory response in M. salmoides were carried out during the ammonia stress test and feeding test. The results demonstrated that the LC50 for 24 h, 48 h, 72 h, and 96 h under ammonia stress in M. salmoides were 25.78 mg/L, 24.40 mg/L, 21.90 mg/L, and 19.61 mg/L, respectively. Under ammonia stress, the structures of the tissues were damaged, and the GSH content decreased, while the MDA content increased with the increase in stress time and ammonia concentration. The NO content fluctuated significantly after the ammonia nitrogen stress. In the 15-day feeding test, with the increased NCG addition amount and feeding time, the GSH content increased while the MDA and NO contents decreased gradually in the NCG addition groups (NL group: 150 mg/kg; NM group: 450 mg/kg; NH group: 750 mg/kg) when compared with their control group (CK group: 0 mg/kg). In the ammonia toxicology test after feeding, the damage to each tissue was alleviated in the NL, NM, and NH groups, and the contents of GSH, MDA, and NO in most tissues of the NH group were significantly different from those in the CK group. The results suggested that ammonia stress caused tissue damage in M. salmoides, provoking oxidative stress and inflammatory response. The addition of NCG to the feed enhances the anti-ammonia ability of M. salmoides. Moreover, the gill and liver might be the target organs of ammonia toxicity, and the brain and kidney might be the primary sites where NCG exerts its effects. Our findings could help us to find feasible ways to solve the existing problem of environmental stress in M. salmoides culture.

The Effect of Behavior Couples Therapy on Alcohol and Drug Use Disorder: a Systematic Review and Meta-Analysis.

AIMS: Behavior couples therapy (BCT) is widely considered to be effective in the treatment of substance use disorders. However, the effect size of BCT in different outcome measures, and at different time points requires further study to prove it. METHODS: Systematic searches were performed in various databases. Ultimately, we identified 12 studies, involving 19 randomized controlled trials. We used Hedges' g as the effect size, and all pooled analyses were performed using random-effects models. RESULTS: After treatment, BCT was superior to control conditions (either an active or inactive control group) in frequency of substance use (g = 0.17), substance use consequences (g = -0.28) and relationship satisfaction (g = 0.45). After a 12-month follow-up, BCT remained superior to control conditions in frequency of substance use (g = 0.32), substance use consequences (g = -0.34) and relationship satisfaction (g = 0.31). In addition, BCT was more effective in reducing the frequency of substance use than individual-based treatment (IBT) (g = 0.23). There was no significant relationship between the effect size of BCT and publication year (t = 0.92, P = 0.372), percentage of females (t = -0.02, P = 0.987) or the number of treatment sessions (t = -0.52, P = 0.609). CONCLUSIONS: BCT was superior to the control conditions in all three outcome measures after treatment and at follow-up, and showed a relatively large effect size for relationship satisfaction. Moreover, BCT was superior to IBT in reducing the frequency of substance use.

Causal Roles of Sleep Duration in Osteoporosis and Cardiometabolic Diseases: A Mendelian Randomization Study.

Sleep duration suggests some association with osteoporosis and cardiometabolic diseases, but it is unknown if these associations are causal or confounded. In this two-sample Mendelian randomization (MR) study, we included the largest genome-wide association studies (GWASs) associated with sleep duration and the outcome measures of osteoporosis and cardiometabolic diseases. Finally, 25 single nucleotide polymorphisms (SNPs) associated with short sleep duration and 7 SNPs associated with long sleep duration obtained the genome-wide significance (P < 5 × 10-8) and were used as instrumental variables. Genetic predisposition to short sleep duration was strongly associated with increased risk of coronary artery disease (beta-estimate: 0.199, 95% confidence interval CI: 0.081 to 0.317, standard error SE:0.060, P value = 0.001) and heart failure (beta-estimate: 0.145, 95% CI: 0.025 to 0.264, SE:0.061, P value = 0.017), which were both confirmed by the sensitivity analyses. Both short and long sleep duration may reduce the estimated bone mineral density (eBMD, beta-estimate: -0.086, 95% CI: -0.141 to -0.031, SE:0.028, P value = 0.002 for short sleep duration; beta-estimate: -0.080, 95% CI: -0.120 to -0.041, SE:0.020, P value < 0.0001 for long sleep duration). There was limited evidence of associations between sleep duration and fracture, type 2 diabetes, atrial fibrillation, fasting glucose, fasting insulin, or HbA1c. This study provides robust evidence that short sleep duration is causally associated with high risk of coronary artery disease and heart failure and suggests that short sleep duration should be avoided to prevent these two cardiovascular diseases. Short and long sleep duration show some MR association with reduced eBMD, which indicates that both short and long sleep duration may be prevented to reduce the incidence of osteoporosis.

The effect of exposure and response prevention therapy on obsessive-compulsive disorder: A systematic review and meta-analysis.

This meta-analysis mainly examined the effect size of exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) when compared with different control conditions, and the difference in the efficacy of different variants of ERP in the treatment of OCD. Thirty studies were included, involving 39 randomized controlled trials with 1793 participants, from 30 studies up to January 18, 2022. Hedge's g was calculated using random-effects models. The results showed that ERP had a definite effect on OCD (g = 0.37), and its effect was significant when the control condition was placebo (g = 0.97) or drug (g = 0.59). However, ERP did not show statistical differences with other therapies in improving OCD (g = -0.07). In addition, we found that both therapist and self-controlled exposure (at the same time as the therapist controls, self-control is exercised after the therapy session) and total response prevention can better improve OCD symptoms. In addition, compared with the control group, ERP reduced depression (g = 0.15) and anxiety symptoms (g = 0.23) in patients with OCD. Meta-regression results showed that the longer the length of sessions, the better the treatment effect (t = 2.41, p = 0.022).

The Distribution Pattern of First-Line Anti-Tuberculosis Drug Concentrations between the Blood and the Vertebral Focus of Spinal Tuberculosis Patients.

BACKGROUND: Anti-tuberculosis drug concentrations are critical for the treatment of spinal tuberculosis. The distribution pattern of anti-tuberculosis drugs between the blood and the vertebral focus needs to be further explored. METHODS: A total of 31 spinal tuberculosis patients were prospectively included and then divided into a sclerotic group (15 cases) and a non-sclerotic group (16 cases) according to their preoperative CTs. All patients were treated with 2HERZ/6H2R2Z2 chemotherapy for 4 weeks before the operation. During the operation, blood, normal vertebral bone tissue, and vertebral focus tissue were obtained, processed, and sent to the pharmacology laboratory. The concentration values of four anti-tuberculosis drugs in each sample were obtained in a pharmacology laboratory. RESULTS: There was no significant difference in the concentrations of the four anti-tuberculosis drugs in the blood and the normal vertebral bone tissue between the two groups; however, there was a significant difference in the vertebral focus tissue. There existed a linear correlation of four anti-tuberculosis drug concentrations between the blood and the focus in the non-sclerotic bone group. CONCLUSIONS: The existence of sclerotic bone hinders the anti-tuberculosis drug distribution. In the absence of sclerotic bone in the vertebral focus, there exists a linear relationship of the four anti-tuberculosis drug concentrations between the blood and the vertebral focus of spinal tuberculosis patients.

The mevalonate pathway promotes the metastasis of osteosarcoma by regulating YAP1 activity via RhoA.

Osteosarcoma is the most common malignant bone tumour, and the metastasis of osteosarcoma is an important cause of death. Evidence has shown that the mevalonate pathway is highly activated and is expected to be a new target for tumour therapy. In this study, we investigated the effect of mevalonate signalling on osteosarcoma metastasis and its molecular mechanism. First, we found that the key rate-limiting enzyme of mevalonate signalling, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), was highly expressed in osteosarcoma cells, and inhibition of HMGCR with simvastatin significantly inhibited the motility of 143B cells. Next, we found that YAP1 activity was significantly upregulated in osteosarcoma cells and that YAP1 knockdown inhibited the motility of 143B cells. We also found that the mevalonate pathway regulated the motility of 143B cells by modulating YAP1 phosphorylation and cellular localization. Moreover, we found that the activity of YAP1 was regulated by the mevalonate pathway by modulating the cell membrane localization of RhoA. Finally, we demonstrated that inhibition of the mevalonate pathway notably reduced the lung metastasis of 143B cells, as reflected by the decreased incidence and number of metastatic nodules and the increased survival time of the nude mice. Taken together, our findings suggest that the mevalonate pathway can promote the metastasis of osteosarcoma by activating YAP1 via RhoA. Inhibition of the mevalonate pathway may be a promising therapeutic strategy for osteosarcoma metastasis.

Establishment of hyperammonemia mode in yellow catfish and the mitigation of exogenous L-ornithine-L-aspartate.

Ammonia stress can lead to fish ammonia poisoning. The l-ornithine-l-aspartate (LoLa) has potential value in treating fish hyperammonemia. This study tried to establish a hyperammonemia mode of yellow catfish, which was used to evaluate the effect of LoLa on hyperammonemia. Fish were injected with ammonium acetate and sodium chloride for 3 d to establish model, respectively. Then ammonium acetate group was divided into two groups: one group was further injected with ammonium acetate, another group was injected with LoLa. Sodium chloride group was also divided into two groups: one group was further injected with sodium chloride, another group was injected with LoLa. The experiment continued for 96 h. The results showed that ammonia poisoning could induce serum ammonia content elevated, liver damage (serum aminotransferase activity elevated and liver malondialdehyde accumulation), and up-regulation of cytokine (IL 1, IL 8 and TNFɑ), apoptosis (P53, Bax, Cytochrome c, Caspase 3 and Caspase 9) and autophagy (Dynein, Beclin 1, AKT and PTEN) genes transcription, but LoLa could mitigate the adverse effect of ammonia poisoning. Our results suggesting that LoLa can detoxify ammonia into glutamine and stores it in muscle.

The argininosuccinate synthetase can differentially regulate nitric oxide synthase in yellow catfish Pelteobagrus fulvidraco.

Fish are at high risk of exposure to ammonia in aquaculture systems. When ammonia stress occurs, fish are more prone to disease outbreaks, but the mechanism is not very clear. The argininosuccinate synthetase (ASS) plays an important role in the regulation of urea synthesis and nitric oxide synthesis. We speculated that there must be some relationship between ASS expression and disease outbreak. In this study, ASS was cloned from the yellow catfish. The full-length cDNAs of ASS was 1558 bp, with open reading frames of 1236 bp. The mRNA expression of ASS gene was the highest in liver, kidney and brain. This study consists of two parts: 1) For ammonia challenge in vivo, yellow catfish (15.00 ± 1.50 g) were divided into control group, low ammonia group (1/10 96 h LC50), and high ammonia group (1/2 96 h LC50). The experiment continued for 192 h. The results showed that ammonia stress elevated serum ammonia content, and inhibited urea synthesis enzymes activities but up-regulated the expression levels of related genes except ARG, and induced arginine accumulation and nitric oxide synthase (nNOS and iNOS) different expression, and decreased resistance to Aeromonas hydrophage; 2) For ammonia challenge in vitro, the primary culture of liver cell was divided into four groups: control group, BPP group (Bj-BPP-10c was added as ASS activator), Amm group (96 h LC50), and Amm + BPP group. The experiment continued for 96 h. The results showed that the Bj-BPP-10c can inhibit nNOS activity and improve cell survival rate, and enhance iNOS activity and immune response (lysozyme, complement, respiratory burst, and phagocytic index) by activate ASS when ammonia stress occurred. Our results indicated that targeted regulation of ASS can improve iNOS activity, and enhance the immune response of yellow catfish under ammonia stress.

Glutamine synthetase (GS) deficiency can affect ammonia tolerance of yellow catfish Pelteobagrus fulvidraco.

Glutamine synthetase (GS) plays a crucial role in the regulation of glutamine synthesis in fish which is a very effective ammonia detoxification strategy. In this study, the full-length GS was cloned from the liver of yellow catfish. The full-length cDNA sequence of GS was 1928 bp in length and encoded 371 amino acids. The amino acid sequence of GS showed high homology (99%) with that of channel catfish. The highest mRNA expression of GS was found in the brain of yellow catfish. Acute ammonia stress (96 h LC50) significantly increased ammonia levels in plasma, liver, and brain, and GS gene expression was significantly up-regulated in the liver and brain. RNA interference inhibited the GS mRNA expression level in primary cultured hepatocytes after acute ammonia stress and reduced hepatocyte survival rate. It is suggested that GS plays a key role in ammonia detoxification in yellow catfish by regulating glutamine synthesis.

Causal associations of circulating adiponectin with cardiometabolic diseases and osteoporotic fracture.

Circulating adiponectin shows some relationships with the occurrence of cardiometabolic diseases and osteoporotic fracture, but little is known about their causal associations. This two-sample Mendelian randomization (MR) study aims to explore the causal roles of circulating adiponectin in cardiometabolic diseases and osteoporotic fracture. We used 15 single nucleotide polymorphisms associated with circulating adiponectin as the instrumental variables. Inverse variance weighted, weighted median and MR-Egger regression methods were applied to study the causal associations. The results found that high circulating adiponectin was causally associated with reduced risk of type 2 diabetes (beta-estimate: -0.030, 95% CI: -0.048 to -0.011, SE: 0.009, P-value = 0.002) and may be the risk factor of coronary artery disease (beta-estimate: 0.012, 95% CI: 0.001 to 0.023, SE: 0.006, P-value = 0.030). No causal associations were seen between circulating adiponectin and other outcomes including heart failure, atrial fibrillation, cerebral ischemia, intracerebral hemorrhage or osteoporotic fracture. This study found the potential causal roles of high circulating adiponectin in reduced risk of type 2 diabetes and increased risk of coronary artery disease, which may help prevent and treat these two diseases.