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Fermentation is a promising approach for improving the utilization of soybean meal (SM) by aquaculture fish, and the strain is the core of microbial fermentation processes. Herein, Pediococcus pentosaceus YC64, an autochthonous probiotic isolated from the intestine of Nile tilapia (Oreochromis niloticus), was applied to the fermentation of raw SM. In an eight-week feeding trial, tilapia juveniles were divided into two treatments fed on diets with 0 % (Control) and 100 % of SM protein replaced by fermented SM (FSM). Results showed that solid-state fermentation improved SM quality indicated by increased acid-soluble protein contents. Fish fed the FSM diet had significantly higher weight gain, feed efficiency, and protein efficiency compared to those fed the SM diet. Furthermore, whole-body protein content significantly increased in the FSM-fed fish, accompanied with the increased amino acid transport and reduced protein catabolism. Texture profile analysis indicated that fish fed the FSM diet had reduced muscle hardness compared with the control, which was associated with changes in collagen deposition and myofiber development. Moreover, feeding an FSM diet enhanced goblet cell proliferation and stimulated mucin secretion, ultimately leading to improved intestinal tight junctions and reduced inflammatory response. Besides, the FSM diet feeding altered intestinal microbiota community, characterized by increased abundance of Pediococcus. Overall, P. pentosaceus YC64 exhibits promise as a fermentation strain in the production of FSM. The FSM performed better than SM in improving the growth performance, feed utilization, and intestine health of Nile tilapia.

The power battery in an electric vehicle is an essential part, and the damage to the battery will have a substantial impact on its thermal characteristics. In order to improve the reliability of the air-cooled lithium-ion battery packs in the high temperature environments, this paper offers a more useful and general optimization strategy for the design of the thermal management system for the batteries which have a damaged battery. To ensure the optimal heat dissipation and prolong the battery string operation, the damaged batteries should be swapped out with the backup batteries. The relationship between the target and the design variables which was established using the quadratic polynomial response function is examined. The experimental cases are selected using the optimal Latin hypercube design approach. After optimizing through the multi-island genetic approach, the error between the simulation results and the prediction results is only 0.06 %. The maximum temperature and the maximum temperature difference of the ideal structure are reduced by 4.58 % and 28.05 %, respectively. Then, the backup battery is selected as the sole battery that has the highest temperature of the ideal structure, and each broken battery is replaced by the backup battery when the damaged position is determined. Finally, a parametric equation connecting the temperature and the flow rate is created, and the inlet flow rate is tuned to match the optimal heat dissipation state of the battery pack. The results of the battery thermal management system having a damaged battery in various situations have an important significance for adjusting the operating conditions of the cooling system for the batteries.

Abstract Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating glucose and lipid metabolic homeostasis. However, the action of citrate in regulating nutrient metabolism in fish remains poorly understood. Here, we investigated the effects of dietary sodium citrate on growth performance and systematic energy metabolism in juvenile Nile tilapia (Oreochromis niloticus). A total of 270 Nile tilapia (2.81 ± 0.01 g) were randomly divided into three groups (3 replicates per group, 30 fish per replicate) and fed with control diet (35% protein and 6% lipid), 2% and 4% sodium citrate diets, respectively, for 8 weeks. The results showed that sodium citrate exhibited no effect on growth performance (P > 0.05). The whole-body crude protein, serum triglyceride and hepatic glycogen contents were significantly increased in the 4% sodium citrate group (P < 0.05), but not in the 2% sodium citrate group (P > 0.05). The 4% sodium citrate treatment significantly increased the serum glucose and insulin levels at the end of feeding trial and also in the glucose tolerance test (P < 0.05). The 4% sodium citrate significantly enhanced the hepatic phosphofructokinase activity and inhibited the expression of pyruvate dehydrogenase kinase isozyme 2 and phosphor-pyruvate dehydrogenase E1 component subunit alpha proteins (P < 0.05). Additionally, the 4% sodium citrate significantly increased hepatic triglyceride and acetyl-CoA levels, while the expressions of carnitine palmitoyl transferase 1a protein were significantly down-regulated by the 4% sodium citrate (P < 0.05). Besides, the 4% sodium citrate induced crude protein deposition in muscle by activating mTOR signaling and inhibiting AMPK signaling (P < 0.05). Furthermore, the 4% sodium citrate significantly suppressed serum aspartate aminotransferase and alanine aminotransferase activities, along with the lowered expression of pro-inflammatory genes, such as nfκb, tnfα and il8 (P < 0.05). Although the 4% sodium citrate significantly increased phosphor-nuclear factor-kB p65 protein expression (P < 0.05), no significant tissue damage or inflammation occurred. Taken together, dietary supplementation of sodium citrate could exhibit a double-edged effect in Nile tilapia, with the positive aspect in promoting nutrient deposition and the negative aspect in causing hyperglycemia and insulin resistance.

Carbohydrates have a protein sparing effect, but long-term feeding of a high-carbohydrate diet (HCD) leads to metabolic disorders due to the limited utilization efficiency of carbohydrates in fish. How to mitigate the negative effects induced by HCD is crucial for the rapid development of aquaculture. Uridine is a pyrimidine nucleoside that plays a vital role in regulating lipid and glucose metabolism, but whether uridine can alleviate metabolic syndromes induced by HCD remains unknown. In this study, a total of 480 Nile tilapia (Oreochromis niloticus) (average initial weight 5.02 ± 0.03 g) were fed with 4 diets, including a control diet (CON), HCD, HCD + 500 mg/kg uridine (HCUL) and HCD + 5,000 mg/kg uridine (HCUH), for 8 weeks. The results showed that addition of uridine decreased hepatic lipid, serum glucose, triglyceride and cholesterol (P

Abstract The THO complex (THOC) is ubiquitously involved in RNA modification and various THOC proteins have been reported to regulate tumor development. However, the role of THOC3 in lung cancer remains unknown. In this study, we identified that THOC3 was highly expressed in lung squamous cell carcinoma (LUSC) and negatively associated with prognosis. THOC3 knockdown inhibited LUSC cell growth, migration, and glycolysis. THOC3 expression was regulated by TRiC proteins, such as CCT8 and CCT6A, which supported protein folding. Furthermore, THOC3 could form a complex with YBX1 to promote PFKFB4 transcription. THOC3 was responsible for exporting PFKFB4 mRNA to the cytoplasm, while YBX1 ensured the stability of PFKFB4 mRNA by recognizing m5C sites in its 3′UTR. Downregulation of PFKFB4 suppressed the biological activities of LUSC. Collectively, these findings suggest that THOC3, folded by CCT proteins can collaborate with YBX1 to maintain PFKFB4 expression and facilitate LUSC development. Therefore, THOC3 could be considered as a novel promising therapeutic target for LUSC.

Lysophospholipids (LPLs) and bile acids (BA) are commonly used as emulsifiers in aquaculture. This study investigated the effects of dietary supplementation of LPLs or BA on the growth performance, lipid deposition, and intestinal health of largemouth juveniles. Fish were randomly allotted into three groups in quadruplicate and fed with a basal diet (CON) or diets containing 300 mg/kg LPLs (LPLs), or 300 mg/kg commercially available BA product (BA) for 8 weeks. The results showed that compared with the control group, LPLs and BA supplemented groups showed a higher weight gain trend, and LPLs supplementation promoted the protein deposition in fish body. Both BA and LPLs supplementations helped to maintain liver health by decreasing the activities of aspartate aminotransferase and alanine aminotransferase in serum. Besides, LPLs supplementation decreased overall lipid deposition in terms of mesenteric fat index and liver lipid content. Furthermore, LPLs supplementation showed unique advantage in improving intestinal barrier, as characterized by the increased villus length and higher expression of the tight junction protein zo-1 expression. LPLs supplementation also increased the alpha diversity index and the abundances of Proteobacteria in the intestinal microbiota which is positively correlated with the abundance of SCFA in the gut. These findings will promote the application of novel feed additives and especially provide a basis for the rational selection of emulsifiers in the aquaculture industry.

PurposeTo explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping.MethodsA total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc.ResultsVAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05).ConclusionsIn this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

Although several investigations have demonstrated the beneficial effects of chrysin (CH), there is limited information on its supportive effects on rainbow trout (Oncorhynchus mykiss) physiology. In this work, fish were fed with pellets containing 0, (CH0) 100 (CH100), 300 (CH300), 500 (CH500) and 700 (CH700) mg/kg chrysin for 56 days, then the specimens weighed and were exposed to 14-day crowding stress. Innate immune responses, antioxidant capacity, hematology indices, and biochemical parameters were tested before and after crowding stress. The final weight (FW), weight gain (WG), and specific growth rate (SGR) increased, and feed conversion ratio (FCR) decreased in the groups fed diets containing CH300-CH700 compared to control group. Also, the optimum dose for maximum and minimum SGR and FCR were obtained at 470 and 490 mg CH (P < 0.05), according to the polynomial regression test, respectively. There was an interaction between dietary CH and crowding stress on immune responses, antioxidant defense, hematological and serum biochemical parameters. Before stress, serum and mucus immune responses [lysozyme and alternative complement (ACH50) activity, and total immunoglobulin (Ig)] were increased in CH300 group (P < 0.05). After stress, immunological activities were improved by diets supplemented with 300–700 mg/kg of chrysin. Before stress, red blood cell (RBC) count, percentage of hematocrit (HCT), blood leukocyte (WBC) count, and monocyte (MON) count clearly increased in the CH300 group (P < 0.05). After stress, hematological parameters were enhanced in the CH-treated fish compared to the control. The lowest serum biochemical parameters (liver enzymes, and glucose) values were noticed in CH500 treatment before stress, except for cortisol. After stress, serum biochemical parameters in response to all dietary treatments significantly decreased, except for aspartate aminotransferase (AST) (P < 0.05). Before stress, antioxidant enzymes activities significantly improved in fish fed with diets containing 300 and 500 mg of CH (P < 0.05). After stress, administration of 300–700 mg CH remarkably boosted antioxidant enzymes activities (P < 0.05). MDA value decreased in response to diets containing 300–700 mg CH, before and after stress. In summary, CH300 and CH500 diets more effectively boosted growth performance and reduced the harmful effects of crowding on health status of the rainbow trout.

This study investigated the effects of yellow mealworm meal (YM) replacing soybean meal (SBM) at different proportions (0%, 15%, 30% and 45%, referred as YM0, YM15, YM30 and YM45, respectively) on the flesh quality of Nile tilapia. A total of 360 fish (70.0 ± 0.12 g) were randomly divided into 4 groups (3 tanks per group). Fish were fed the experimental diet twice daily for 10 wk. The results showed that muscle protein content significantly decreased in YM30 and YM45, while the lipid content significantly decreased in YM45 (P

ABSTRACT Ectomycorrhizal fungi play an irreplaceable role in phosphorus cycling. However, ectomycorrhizal fungi have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. Endofungal bacteria in ectomycorrhizal fruiting bodies are always closely related to the ecological function of ectomycorrhizal fungi. In this study, we explore endofungal bacteria in the fruiting body of Tylopilus neofelleus and their function during the absorption of chelated inorganic phosphorus by host pine through the ectomycorrhizal system. The results showed that the endofungal bacterial microbiota in the fruiting body of T. neofelleus might be related to the dissolution of chelated inorganic phosphorus in soil. The soluble phosphorus content in the combined system of T. neofelleus and endofungal bacteria Bacillus sp. strain B5 was five times higher than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment in the dissolution experiment of chelated inorganic phosphorus. The results showed that T. neofelleus not only promoted the proliferation of Bacillus sp. strain B5 in the combined system but also improved the expression of genes related to organic acid metabolism, as assesed by transcriptomic analysis. Lactic acid content was five times higher in the combined system than the sum of T. neofelleus-only treatment and Bacillus sp. strain B5-only treatment. Two essential genes related to lactate metabolism of Bacillus sp. strain B5, gapA and pckA, were significantly upregulated. Finally, in a pot experiment, we verified that T. neofelleus and Bacillus sp. strain B5 could synergistically promote the absorption of chelated inorganic phosphorus by Pinus sylvestris in a ternary symbiotic system. IMPORTANCE Ectomycorrhizal fungi (ECMF) have a limited ability to dissolve chelated inorganic phosphorus, which is the main component of soil phosphorus. In the natural environment, the extraradical hyphae of ECMF alone may not satisfy the phosphorus demand of the plant ectomycorrhizal system. In this study, our results innovatively show that the ectomycorrhizal system might be a ternary symbiont in which ectomycorrhizal fungi might recruit endofungal bacteria that could synergistically promote the mineralization of chelated inorganic phosphorus, which ultimately promotes plant phosphorus absorption by the ectomycorrhizal system.

Abstract PKM2 is an important regulator of the aerobic glycolysis that plays a vital role in cancer cell metabolic reprogramming. In general, Trib2 is considered as a “pseudokinase”, contributing to different kinds of cancer. However, the detailed roles of TRIB2 in regulating cancer metabolism by PKM2 remain unclear. This study demonstrated that TRIB2, not a “pseudokinase”, has the kinase activity to directly phosphorylate PKM2 at serine 37 in cancer cells. The elevated pSer37-PKM2 would subsequently promote the PKM2 dimers to enter into nucleus and increase the expression of LDHA, GLUT1, and PTBP1. The aerobic glycolysis is then elevated to promote cancer cell proliferation and migration in TRIB2- or PKM2-overexpressed cultures. The glucose uptake and lactate production increased, but the ATP content decreased in TRIB2- or PKM2-treated cultures. Experiments of TRIB2−/− mice further supported that TRIB2 could regulate aerobic glycolysis by PKM2. Thus, these results reveal the new kinase activity of TRIB2 and its mechanism in cancer metabolism may be related to regulating PKM2 to promote lung cancer cell proliferation in vitro and in vivo, suggesting promising therapeutic targets for cancer therapy by controlling cancer metabolism.

ObjectiveEvidence from observational studies suggests that Sjögren’s syndrome (SS) may contribute to an elevated risk of Parkinson’s disease (PD) and dementia. However, few studies have been undertaken to summarize and assess the consistency of the data quantitatively. Therefore, we evaluated the risk of dementia and PD in SS patients through a systematic review and meta-analysis approach.MethodsTwo reviewers independently conducted a systematic search of PubMed, Embase, and Web of Science databases (updated to February 14, 2022) to identify published literature on the association between SS and dementia or PD. The risk estimates of dementia or PD in patients with SS were pooled using fixed or random-effects models.ResultsOf the 631 studies initially searched, 10 were eventually included. Pooled results suggested that the risk of developing dementia significantly increased in patients with SS (HR = 1.24, 95% CI: 1.15–1.33, P < 0.001), and such risk in females with SS was similar to that in males. The risk of PD was 1.36 times higher in SS (HR = 1.36, 95% CI: 1.23–1.50, P < 0.001). The association between SS and PD risk appeared to occur primarily in female patients (female: HR = 1.28, 95% CI: 1.21–1.35; P < 0.001 vs. male: HR = 1.00, 95% CI: 0.87–1.16, P = 0.962, respectively). No significant effect of age was observed on the risk of developing PD and dementia in SS patients.ConclusionOur study supports that people with SS are at higher risk of PD and dementia than the general population. Further studies are needed to elucidate the underlying mechanisms and to assess whether interventions for SS have the potential to affect dementia and PD development.

BackgroundThe association between shift work, night work, and the risk of dementia are conflicting in the literature.ObjectivesThis study was performed to obtain evidence on the potential relationship between shift work, night work, and dementia.MethodsTo investigate the link between shift work, night work, and dementia, we systematically searched PubMed, Embase, and Web of Science from inception to January 1, 2022. The eligibility of the retrieved records and extracted data were independently reviewed by two researchers. The Preferred Reporting Items for Systematic Evaluations and Meta-Analyses (PRISMA) statement was followed. STATA 16.0 was used to conduct the meta-analysis.ResultsA total of four studies involving 103,104 participants were included in this meta-analysis. Pooled results indicated that night shift workers had a 12% increased risk of dementia compared to subjects without night work (HR = 1.12, 95% CI 1.03–1.23, P = 0.094). Shift work was not significantly associated with dementia risk (HR: 1.09, 95% CI: 0.83–1.43, P = 0.546), but the effect of shift work on dementia risk appeared to increase with age, with a correlation observed among workers older than 50 years (HR = 1.31; 95% CI: 1.03–1.68, P = 0.030).ConclusionThe data presented in our study suggest that night work may be a risk factor for dementia. More prospective studies with objective exposure measurements are required to further confirm this result.Systematic review registrationhttps://doi.org/10.37766/inplasy2022.6.0079, identifier: INPLASY202260079.

Long non-coding RNAs (lncRNAs) modulate cell proliferation, cycle, and apoptosis. However, the role of lncRNA-WFDC21P in the tumorigenesis of triple-negative breast cancer (TNBC) remains unclear. Results of this study demonstrated that WFDC21P levels significantly increased in TNBC, which was associated with the poor survival of patients. WFDC21P overexpression significantly promoted TNBC cell proliferation and metastasis. WFDC21P interacted with miR-628-5p, which further suppressed cell proliferation and metastasis by negatively regulating Smad3-related gene expression. Recovery of miR-628-5p weakened the roles of WFDC21P in promoting the growth and metastasis of TNBC cells. Moreover,N6-methyladenosine (m6A) modification upregulated WFDC21P expression in the TNBC cells. WFDC21P and its m6A levels were increased after methyltransferase like 3 (METTL3) overexpression but reduced after METTL3 silencing. The proliferation and metastasis of TNBC cells were promoted by METTL3 overexpression but suppressed by METTL3 silencing. This study demonstrated the vital roles of WFDC21P and its m6A in regulating the proliferation and metastasis of TNBC cells via the WFDC21P/miR-628/SMAD3 axis.

In organic solar cells (OSCs), electron donor–acceptor materials are key factors influencing device performance. However, traditional experimental methods for developing new, high-performance materials are often time-consuming, costly and inefficient. To accelerate the development of novel OSC donor–acceptor materials, we constructed a database of 547 donor–acceptor pairs and derived 30 easily obtainable molecular structure descriptors through transformation screening. Using the long short-term memory (LSTM) network model, belonging to deep learning, we tuned the LSTM model with grid search for optimal hyperparameters, and predicted the power conversion efficiency (PCE), open-circuit voltage, short-circuit current density and fill factor. The SHapley Additive exPlanations analysis revealed that the number of rotatable bonds and the presence of two or more rings in acceptor molecules positively impact PCE. We then systematically fragmented and recombined molecules in the constructed database, creating 142 560 donor molecules and 61 732 acceptor molecules. The tuned LSTM model predicted photovoltaic parameters for these new donor–acceptor pairs. After excluding the donor–acceptor pairs in the database, we identified 7632 novel pairs with a predicted PCE greater than 18.00%, including five pairs exceeding 18.50%, with the maximum PCE of 18.52%. This method facilitates the cost-effective design and rapid, accurate prediction of OSC material performance, enabling efficient screening of high-performance candidates. [ABSTRACT FROM AUTHOR]

Some of the gas turbine components are exposed to high temperature corrosion. Therefore, the life cycle of gas turbine is directly affected by the durability of the components. The blades of the gas turbine are protected by film cooling holes under the condition of combining with thermal barrier coating (TBC) system. The TBC systems improve durability of the high temperature components under the condition of increasing the operating temperature. In order to improve the durability of TBC system, simulation and optimization methods were studied in this paper. Firstly, discussed a theoretical model under the thermal and mechanical loading conditions. In the following step, the hole deformations with the various thermo-mechanical conditions induced by high temperature environment and centripetal force due to rotation of the blade were optimized by design of experiments (DOE) method, in order to improve the durability of TBC system. Next, the deformations subjected to thermo-mechanical cycling induced by high temperature environment and vibration due to real operating condition were discussed. The results show that the effect of vibration is not significant compared to the effect of the centripetal force. Keywords: Thermally grown oxide, Gas turbine blade, Vibration, Optimization

Five new oleanane-type triterpenoid saponins (1–5), together with 24 known saponins (6–29) were isolated from the fruit of Acanthopanax senticosus. Their structures were determined by extensive spectroscopic analysis, including 1D, 2D nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), in combination with chemical methods (acid hydrolysis). The neuroinflammation model was established by lipopolysaccharide (LPS)-induced BV2 microglia, and the neuroprotective effects of all compounds (1–29) were evaluated.

Since high-fat diet (HFD) intake elevates liver cholesterol and enhanced cholesterol-bile acid flux alleviates its lipid deposition, we assumed that the promoted cholesterol-bile acid flux is an adaptive metabolism in fish when fed an HFD. The present study investigated the characteristic of cholesterol and fatty acid metabolism in Nile tilapia (Oreochromis niloticus) after feeding an HFD (13% lipid level) for four and eight weeks. Visually healthy Nile tilapia fingerlings (average weight 3.50±0.05 g) were randomly distributed into four treatments (4-week control diet or HFD and 8-week control diet or HFD). The liver lipid deposition and health statue, cholesterol/bile acid, and fatty acid metabolism were analyzed in fish after short-term and long-term HFD intake. The results showed that 4-week HFD feeding did not change serum alanine transaminase (ALT) and aspartate transferase (AST) enzyme activities, along with comparable liver malondialdehyde (MDA) content. But higher serum ALT and AST enzyme activities and liver MDA content were observed in fish fed 8-week HFD. Intriguingly, remarkably accumulated total cholesterol (mainly cholesterol ester, CE) was observed in the liver of fish fed 4-week HFD, along with slightly elevated free fatty acids (FFAs) and comparable TG contents. Further molecular analysis in the liver showed that obvious accumulation of CE and total bile acids (TBAs) in fish fed 4-week HFD was mainly attributed to the enhancement of cholesterol synthesis, esterification, and bile acid synthesis. Furthermore, the increased protein expressions of acyl-CoA oxidase 1/2 (Acox1 and Acox2), which serve as peroxisomal fatty acid β-oxidation (FAO) rate-limiting enzymes and play key roles in the transformation of cholesterol into bile acids, were found in fish after 4-week HFD intake. Notably, 8-week HFD intake remarkably elevated FFA content (about 1.7-fold increase), and unaltered TBAs were found in fish liver, accompanied by suppressed Acox2 protein level and cholesterol/bile acid synthesis. Therefore, the robust cholesterol-bile acid flux serves as an adaptive metabolism in Nile tilapia when fed a short-term HFD and is possibly via stimulating peroxisomal FAO. This finding enlightens our understanding on the adaptive characteristics of cholesterol metabolism in fish fed an HFD and provides a new possible treatment strategy against metabolic disease induced by HFD in aquatic animals.

High level of carbohydrate in aquafeed could achieve cost-sparing effect, but it may cause adverse effects on flesh quality of aquatic products. An eight-week trial was conducted to investigate whether oligosaccharides-supplementation, including Galacto-oligosaccharides (GOS) and xylo-oligosaccharide (XOS), could systematically improve the growth performance, texture characteristics and nutrition composition of Nile tilapia fed with high-carbohydrate diet. The results indicated that GOS-supplementation improved the amino acid composition, while XOS-supplementation showed beneficial effects on growth performance. High-carbohydrate diet had adverse effects on fillet texture, while oligosaccharide-supplementation regulated the expression of muscle development-related genes to help restoring muscle texture properties. Furthermore, either high-carbohydrate or addition of oligosaccharides could change the intestinal microbiota composition and their metabolites. Further correlation analysis suggested that intestinal microbiota may account for the improvement in fish growth condition and texture characteristics. Application of oligosaccharides may be an innovative strategy for flesh quality modulation in aquaculture.

Probiotic administration is a potential strategy against enteric pathogen infection in either clinical treatment or animal nutrition industry, but the administration duration of probiotics varied and the underlying mechanisms remain unclear. A strain (YC) affiliated to Pediococcus pentosaceus, a commonly used probiotic, was isolated from fish gut and the potential role of YC against Aeromonas hydrophila was detected in zebrafish. We found that 3- or 4-week YC administration (YC3W or YC4W) increased the resistance against A. hydrophila while 1- or 2-week treatment (YC1W or YC2W) did not. To determine the possible reason, intestinal microbiota analysis and RNAseq were conducted. The results showed that compared with CON and YC1W, YC4W significantly increased the abundance of short-chain fatty acids (SCFAs) producing bacteria and elevated the gene expression of nlrp3. Higher butyrate content and enhanced expression of IL1β were subsequently found in YC4W. To identify the causal relationship between butyrate and the higher pathogen resistance, different concentrations of sodium butyrate (SB) were supplemented. The results suggested that 10 mmol/kg SB addition mirrored the protective effect of YC4W by increasing the production of IL-1β. Furthermore, the increased IL-1β raised the percentage of intestinal neutrophils, which endued the zebrafish with A. hydrophila resistance. In vivo knockdown of intestinal il1b eliminated the anti-infection effect. Collectively, our data suggested that the molecular mechanism of probiotics determined the administration duration, which is vital for the efficiency of probiotics. Promoting host inflammation by probiotic pretreatment is one potential way for probiotics to provide their protective effects against pathogens.

The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.

Diet and host genetics influence the composition of intestinal microbiota, yet few studies have compared the function of intestinal microbiota in the diet- or genotype-induced lipid deposition, which limits our understanding of the role of intestinal bacteria in metabolic disorders. The lipid accumulation in wild-type zebrafish fed with control (CON) or high-fat (HF) diet and two gene-knockout zebrafish lines (cpt1b–/– or pparab–/–) fed with control diet was measured after a 4-week feeding experiment. The intestinal microbiota composition of these groups was investigated using 16S ribosomal RNA (rRNA) gene sequencing (DNA-based) and 16S rRNA sequencing (RNA-based). The HF diet or deficiency of two genes induced more weight gain and higher triglyceride content in the liver compared with their control group. 16S rRNA gene sequencing (DNA-based) indicated the decreased abundance of Proteobacteria in the HF group compared with CON, but there was no significant difference in bacterial α diversity among treatments. 16S rRNA sequencing (RNA-based) confirmed the decreased abundance of Proteobacteria and the bacterial α diversity in the HF group compared with CON. Deficiency of cpt1b or pparab showed less change in microbiota composition compared with their wild-type group. Intestinal microbiota of each group was transferred to germ-free zebrafish, and the quantification of Nile red staining indicated that the intestinal microbiota of the HF group induced more lipid accumulation compared with CON, whereas intestinal microbiota of cpt1b–/– and pparab–/– zebrafish did not. The results showed that RNA-based bacterial sequencing revealed more bacterial alteration than DNA-based bacterial sequencing. HF diet had a more dominant role in shaping gut microbiota composition to induce lipid accumulation compared with the gene-knockout of cpt1b or pparab in zebrafish, and the transplant of intestinal microbiota from HF-fed fish induced more lipid deposition in germ-free zebrafish. Together, these data suggested that a high-fat diet exerted a more dominant role over the deletion of cpt1b or pparab on the intestinal bacterial composition, which corresponded to lipid accumulation.

To optimize the spatial distribution of cotton bolls and to increase the yield, the relationship between yield components and boll spatial distribution was investigated among different Bt (Bacillus thuringensis) cotton varieties. A five-year field experiment was conducted to reveal the reasons for the differences in lint yield and fiber quality across three Bt cotton varieties with different yield formations from 2013 to 2017. The lint yield of Jiman 169 (the average yield from 2013–2017 was 42.2 g/plant) was the highest, i.e., 16.3 and 36.9% higher than Lumianyan 21 (L21) and Daizimian 99B (99B), respectively. And the differences in boll weight among the three cultivars were similar to the lint yield, while the others yield components were not. So the increase in lint yield was mainly attributed to the enlargement in boll weight. However, the change in fiber quality was inconsistent with the lint yield, and the quality of L21 was significantly better than that of Jimian 169 (J169) and 99B, which was caused by the diversity of boll spatial distribution. Compared with 99B, the loose-type J169 had the highest number of large bolls in inner positions; the tight-type L21 had a few large bolls and the highest number of lower and middle bolls. And approximately 80.72% of the lint yield was concentrated on the inner nodes in Jiman 169, compared with 77.44% of L21 and 66.73% of 99B during the five-year experiment. Although lint yield was significantly affected by the interannual changes, the lint yield of J169 was the highest and the most stable, as well as its yield components. These observations demonstrated the increase in lint yield was due to the increase in boll weight, and the large bolls and high fiber quality were attributed to the optimal distribution of bolls within the canopies.

The overconsumption of carbohydrates induces oxidative stress and lipid accumulation in the liver, which can be alleviated by modulation of intestinal microbiota; however, the underlying mechanism remains unclear. Here, we demonstrated that a strain affiliated with Lactobacillus plantarum (designed as MR1) efficiently attenuated lipid deposition, oxidative stress, as well as inflammatory response, which are caused by high-carbohydrate diet (HC) in fish with poor utilization ability of carbohydrates. Serum untargeted metabolome analysis indicated that pyrimidine metabolism was the significantly changed pathway among the groups. In addition, the content of serum uridine was significantly decreased in the HC group compared with the control group, while it increased by supplementation with L. plantarum MR1. Further analysis showed that addition of L. plantarum MR1 reshaped the composition of gut microbiota and increased the content of intestinal acetate. In vitro experiment showed that sodium acetate could induce the synthesis of uridine in hepatocytes. Furthermore, we proved that uridine could directly ameliorate oxidative stress and decrease liver lipid accumulation in the hepatocytes. In conclusion, this study indicated that probiotic L. plantarum MR1 ameliorated high-carbohydrate diet-induced hepatic lipid accumulation and oxidative stress by increasing the circulating uridine, suggesting that intestinal microbiota can regulate the metabolism of nucleotides to maintain host physiological homeostasis.

L-carnitine is a functional aquafeed additive for enhancing lipid catabolism by elevating mitochondrial fatty acid β-oxidation and modulating energy metabolism to provide a “protein sparing effect”. However, results on the effects of dietary l-carnitine on nutrient metabolism in fish are still conflicting. We explored comprehensively the effects of dietary l-carnitine on energy metabolism in Nile tilapia. We fed Nile tilapia for eight weeks with diets supplemented with l-carnitine or not. We conducted metabolic tracking tests by intraperitoneally injecting individual fish with 14C-labeled palmitic acid (PA), glucose (Glu) and an amino acid mixture (AAs). After the feeding trial, insignificant growth-promoting effect of l-carnitine was obtained in treated fish. However, l-carnitine significantly reduced the lipid content in whole body and muscle accompanied by increasing the free carnitine concentration and fatty acid β-oxidation efficiency. Moreover, l-carnitine elevated concentrations of serum glucose, pyruvate and lactate, and increased glycogen and protein deposition in muscle. These results suggest that ingested glucose and protein prefer to be reserved in carnitine-fed fish with sufficient fatty acids oxidation for energy. Nevertheless, after a 14C-labeled single nutrient injection, carnitine-fed fish showed a higher oxidation rate of [1-14C]-PA, d-[1-14C]-Glu and l-[14C (U)]-AAs. Our study indicates that, the effects of l-carnitine on nutrient metabolism are correlated with the abundance of individual macronutrients such that an inadequate lipid supply would cause dietary l-carnitine supplementation to elevate higher breakdown of glucose and protein for energy generation. The present study provides new insights on the regulation mechanism of l-carnitine on nutrient metabolism in fish.

ABSTRACT An efficient energy harvesting mechanism is likely critical for animals in their natural environment. Intestinal microbiota enriched by a high-fat diet aid in lipid accumulation, a strategy likely evolved for energy harvest in mammals. However, whether this strategy is conserved among vertebrate organisms remains unclear. A bacterial strain (S1), enriched on soybean oil rich medium, was isolated from the gut of Nile tilapia and demonstrated to be a member of the Citrobacter genus. Although a high-fat diet increased the number of Citrobacter spp., these bacteria were not abundant in the intestine by high-throughput sequencing. Addition of bacterium S1 to a high-fat diet modulated intestinal microbial composition and increased high-fat diet-induced lipid accumulation in mesenteric adipose tissue, accompanied by (i) increased triglyceride absorption efficiency and triglyceride reesterification and (ii) increased intestinal permeability. Collectively, our results provide evidence that specific intestinal bacteria aid the host in harvesting more energy from a high-fat diet in fish. Furthermore, the results from the present study also suggest that nondominant bacteria in the gut may play an important role in regulating host metabolism. IMPORTANCE This study shows that the ability of gut microbiota members to enhance host energy harvest from a high-fat diet is a conserved feature of host-microbe interactions in fish, as in mammals. It also underscores that gut microbiota members are able to significantly impact host biology even when at low abundance.

High-fat diet (HFD) caused some adverse effects in farmed fish, thus the adaptation to HFD in fish is an important research topic. This study was conducted to examine the roles of carnitine and its related mitochondrial fatty acid β-oxidation (FAO) in the adaptation to HFD in Nile tilapia. Nile tilapias were fed with HFD (13 %), HFD + mildronate (HFD + MD, inhibitor of carnitine synthesis, 1000 mg/kg body per day) or a normal fat diet (NFD, 7 %) for eight weeks. After the feeding trail, the fish fed with HFD showed higher hepatic free carnitine content and FAO activities, and similar levels of serum triglyceride (TG) and whole body fat. However, the HFD + MD-fed fish remarkably decreased carnitine content and FAO efficiency in tissues than those in the HFD-fed fish, and increased contents of serum free fatty acids (FFA) and TG, whole body fat and hepatic TG. Moreover, the HFD-fed fish upregulated the expressions of the genes associated to FAO, lipid transport and lipolysis. Nevertheless, the fish fed with HFD + MD showed lower transcriptional levels of the genes related to lipolysis and lipid transport, and higher lipogenesis genes. These results indicate that the adaptive changes in the fish fed with HFD were eliminated by dietary MD supplementation, and show that carnitine and its related FAO activity play important roles in the adaptation to HFD in fish. This study illustrates that in the practical usage of HFD in aquaculture, the endogenous carnitine concentration and mitochondrial FAO activities should be important checkpoints. Keywords: Adaptation, L-carnitine, High-fat diet, Lipid deposition, Nile tilapia

The continuous variation of the seasonal influenza viruses, particularly A(H1N1)pdm09, persistently threatens human life and health around the world. In local areas of southwest china, the large time-scale genomic research on A(H1N1)pdm09 is still insufficient. Here, we sequenced 45 whole-genome sequences of influenza A(H1N1)pdm09 viruses in Lincang, China, from 2014 to 2018, by next-generation sequencing technology to characterize molecular mechanisms of their origin and evolution. Our phylogenetic analyses suggest that the A(H1N1)pdm09 strains circulating in Lincang belong to clade 6B and the subclade 6B.1A predominates in 2018. Further, the strains in 2018 possess elevated evolutionary rate as compared to strains in other years. Several newly emerged mutations for HA (hemagglutinin) in 2018 are revealed (i.e., S183P and R221K). Intriguingly, the substitution R221K falls into the RBS (receptor binding site) of HA protein, which could affect antigenic properties of influenza A(H1N1)pdm09 viruses, and another substitution S183P near to RBS with a high covering frequency (11/14 strains) in 2018 is exactly located at the epitope B. Notably, the NA (neuraminidase) protein harbors a new mutation I23T, potentially involved in N-glycosylation. Based on the background with a higher evolutionary rate in 2018 strains, we deeply evaluate the potential vaccine efficacy against Lincang strains and discover a substantive decline of the vaccine efficacy in 2018. Our analyses reaffirm that the real-time molecular surveillance and timely updated vaccine strains for prevention and control of influenza A(H1N1)pdm09 are crucial in the future.

Lipophagy degrades lipid droplets (LDs) through the lysosomal degradative pathway, thus plays important roles in regulating lipid metabolism in mammals. However, information on the existence and functions of lipophagy in fish lipid metabolism is still limited. In the present study, we confirmed the existence of lipophagy by observing the structures of LDs sequestered in autophagic vacuoles in the zebrafish liver cell line (ZFL) via electronic microscopy. Moreover, starved cells increased the mRNA expression of the microtubule-associated protein 1A/1B light chain 3 beta (LC3), which is a marker protein for autophagy and protein conversion from LC3-I to LC3-II. Inhibiting autophagy with chloroquine increased significantly the LDs content and decreased fatty acid β-oxidation and esterification activities in the ZFL cells cultured in the fed state. Furthermore, inhibiting autophagy function downregulated the mRNA expression of the genes and their proteins related to lipid metabolism. Altogether, the present study verified the existence of lipophagy and its essential regulatory roles in lipid metabolism in fish cells.

Background. Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a common type of liver failure with a high mortality. This study aimed at investigating the safety and efficacy of the combination treatment of plasma exchange (PE) and umbilical cord-derived mesenchymal stem cell (UC-MSCs) transplantation for HBV-ACLF patients. Methods. A total of 110 HBV-ACLF patients treated in our hospital from January 2012 to September 2017 were enrolled into this trial and divided into the control group (n=30), UC-MSC group (n=30), PE group (n=30), and UC-MSC + PE group (n=20) based on their treatments. The hepatic function, coagulation, and virological and immunological markers were assessed at baseline and 30, 60, 90, 180, and 360 days. The endpoint outcomes were death and unfavorable outcome (need for liver transplantation or death). Results. The UC-MSC + PE group had the lowest rates of death and unfavorable outcome at 30 days, 60 days, and 90 days posttreatment among the four groups, but the difference did not reach significances. The multivariate logistic regression analysis demonstrated that hemoglobin, prothrombin activity, and MELD (model for end-stage liver disease) score were the independent factors associated with the unfavorable outcome (all P

Leptin is known to inhibit appetite and promote energy metabolism in vertebrates. Leptin resistance (LR) commonly occurs in diet-induced obesity (DIO) in mammals. However, the roles of leptin in the energy homeostasis in DIO animals with LR remain unclear. Here we first verified the high expression of leptin in subcutaneous adipose tissue (SCAT) as in liver in Nile tilapia. Furthermore, we produced two types of DIO Nile tilapia by using a high-carbohydrate diet (HCD) or a high-fat diet (HFD), and confirmed the existence of LR in both models. Notably, we found that HCD-DIO fish retained leptin action in the activation of lipid metabolism and showed LR in glucose metabolism regulation, while this selective leptin action between lipid and glucose metabolism was reversed in HFD-DIO fish. Fasting the fish for 1 week completely recovered leptin actions in the regulation of lipid and glucose metabolism. Therefore, leptin may retain more of its activities in animals with LR than previously believed. Evolutionally, this selective regulation of leptin in nutrients metabolism could be an adaptive mechanism in animals to store surplus calories when different types of food are abundant.

Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be used as a novel fish model for future metabolism studies.

Hypoxia is a common environmental stress factor in aquatic organisms, which varies among fish species. However, the mechanisms underlying the ability of fish species to tolerate hypoxia are not well known. Here, we showed that hypoxia response in different fish species was affected by lipid catabolism and preference for lipid or carbohydrate energy sources. Activation of biochemical lipid catabolism through peroxisome proliferator-activated receptor alpha (Pparα) or increasing mitochondrial fat oxidation in tilapia decreased tolerance to acute hypoxia by increasing oxygen consumption and oxidative damage and reducing carbohydrate catabolism as an energy source. Conversely, lipid catabolism inhibition by suppressing entry of lipids into mitochondria in tilapia or individually knocking out three key genes of lipid catabolism in zebrafish increased tolerance to acute hypoxia by decreasing oxygen consumption and oxidative damage and promoting carbohydrate catabolism. However, anaerobic glycolysis suppression eliminated lipid catabolism inhibition-promoted hypoxia tolerance in adipose triglyceride lipase (atgl) mutant zebrafish. Using 14 fish species with different trophic levels and taxonomic status, the fish preferentially using lipids for energy were more intolerant to acute hypoxia than those preferentially using carbohydrates. Our study shows that hypoxia tolerance in fish depends on catabolic preference for lipids or carbohydrates, which can be modified by regulating lipid catabolism. [ABSTRACT FROM AUTHOR]