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Objective: To develop a clinical prediction model for the risk of distant metastasis in patients with intrahepatic cholangiocarcinoma, to assess the risk of distant metastasis and prognosis of patients, and to explore the efficacy of radiotherapy and chemotherapy in people with different risks of distant metastasis. Method: Clinicopathological data of 15,497 patients diagnosed with intrahepatic cholangiocarcinoma from January 2000 to December 2018were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and all eligible patients were randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Univariate and multivariate logistic regression analyses were performed on the training cohort to identify independent factors for distant metastasis. A prediction model for distant metastasis in patients with intrahepatic ductal carcinoma was constructed based on the independent risk factors for distant metastasis. Receiver Operating Characteristic (ROC) and calibration curves were used to assess the predictive accuracy of the model, and Decision Curve Analysis (DCA) was used to evaluate the clinical utility of the column line graphs.Tumor distant metastasis risk stratification and subgroup survival analysis were performed according to the model, and the benefits of radiotherapy and chemotherapy were explored with the help of the model. Result: Multivariable logistic analysis showed that age, T-stage, N-stage, degree of differentiation, and tumor size were independent risk factors for distant metastasis. The area under the ROC curve (AUC value) was 0.733 (CI95%: 0.713-0.753) and 0.750 (CI95%:0.721-0.780) for the training and validation sets, respectively, and the calibration curves indicated good agreement between predicted and actual values, and the decision curves showed good clinical utility of the model.Subgroup survival analysis suggested that the prognosis is poor in the intermediate and high risk groups, and that radiotherapy and chemotherapy canimprove the prognosis in these groups, with no benefit for the low risk groups. Conclusion: The prediction model of distant metastasis in patients with intrahepatic cholangiocarcinoma based on the SEER database has good prediction accuracy, which helps physicians to assess the risk of distant metastasis and prognosis of patients, thus providing a reference for individualized clinical treatment decisions for patients. Chemotherapy and radiotherapy can significantly improve the survival prognosis of patients with intermediate and high risk of distant metastasis.

Introduction Postoperative delirium(POD) is a common postoperative complication and is associated with numerous adverse outcomes. Advanced age and hip surgery are high risk factors for POD. Both remimazolam tosilate for injection and sevoflurane can be used as sedatives for the maintenance of general anesthesia, but the comparison of their impacts on the incidence of POD has not been reported. This study aims to compare the effect of remimazolam tosilate vernussevoflurane on the incidence of POD in elderly patients undergoing total hip arthroplasty. Methods and Analysis This is a two-arm, parallel, prospective, multicenter, randomized controlled trial. A total of 456 elderly patients at six clinical trial centers in China will be randomly assigned in a 1:1 ratio to receive general anesthesia with remimazolam tosilate or sevoflurane as sedative. The primary outcome measure is the prevalence of POD during the first 4 postoperative days. Secondary outcomes include cognitive function [Mini-Mental State Examination (MMSE)], perioperative pain degree [Visual Analogue Scale (VAS)], postoperative nausea and vomiting (PONV) within 4 days after surgery, recovery time after drug withdrawal, the amount of vasoactive drugs used during operation, length of hospital stay, and in-hospital complications. Ethics and Dissemination The Research Ethics Committee of Qilu Hospital of Shandong University has approved the study protocol (REF: KYLL-202206-25), which is applicable to all research centers. Participant recruitment begins in August 2022. Written informed consent will be obtained from each patient before randomization. The findings will be published in an international peer-reviewed medical journal. Trial Registration The trial has been registered at the Chinese Clinical Trial Registry: ChiCTR2200062455; date of registration: 2022-08-08.

Objective To analyze the clinical and CT imaging features of some patients diagnosed having corona virus disease 2019 (COVID-19) with delayed diagnosis and treatment in Wuhan, Hubei Province for providing a reference for diagnosis and treatment of the disease. Methods A total of 55 patients diagnosed as having COVID-19 by RT-PCT or CT admitted to Wuhan Taikang Tongji COVID-19 Specialized Hospital from 2020-02-15 to 2020-02-25 were retrospectively analyzed. Case data were collected on the first-day history, and the chest CT, blood routine and C-response protein measurements. The clinical manifestations, laboratory examinations and CT imaging features of the patients were analyzed. Results The first symptoms included fever in 33 cases (60.0%), cough in 30(54.6%) expectoration in 7(12.7%), dyspnea in 9(16.4%), chest distress in 15(27.3%), headache in 4(7.3%), fatigue in 33(60.0%), muscle soreness in 10(18.2%) and diarrhea in 7(12.7%). Most of the patients had normal white blood cell, lymphocyte and C-reactive protein levels. The imaging manifestations of CT lesions can be roughly divided into three categories: stripe shadow and consolidation as main clinical manifestations (26 cases, 47.3%), stripe shadow and consolidation mixed with ground glass opacity (10 cases, 18.2%) and patchy ground glass opacity (19 cases, 34.5%). Patients with more than two lobes involved were older, while other clinical and laboratory indexes were not closely related to imaging findings. Conclusions Most of the COVID-19 patients with delayed diagnosis and treatment may improve their clinical symptoms at the time of hospitalization with normal white blood cell, lymphocyte and C-reactive protein levels. Stripe shadow, consolidation, and patchy ground glass opacity are the major CT imaging findings. The patients with extensive lesions are older than these with localized CT imaging findings. DOI: 10.11855/j.issn.0577-7402.2020.05.04

Background: We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori ( H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii ( S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective: To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design: Single-center, prospective randomized controlled study. Methods: A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group ( n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group ( n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results: There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group ( p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group ( p 0.05). The severity of adverse reactions was similar between the two groups ( p > 0.05), and most of them had mild adverse events. Conclusion: Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number: ChiCTR2200056931.

Our team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection.1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed.The intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions.The study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.

BACKGROUND: Early blight caused by Alternaria spp. is amongst the most important diseases in potato. Demethylation inhibitor (DMI) fungicides are widely used to control the disease but long‐term use may decrease its control efficacy due to fungicide resistance. This study investigated the occurrence of difenoconazole resistance in Alternaria spp. and molecular resistant mechanisms. RESULTS: EC₅₀ values of 160 isolates to difenoconazole ranged from 0.026 μg mL⁻¹ to 15.506 μg mL⁻¹ and the frequency of difenoconazole sensitivity formed a non‐normal distribution curve with a major and a minor peak. Isolates with EC₅₀ values of 4.121 and 5.461 μg mL⁻¹ were not controlled effectively at fungicide doses of 50 and 100 μg mL⁻¹. Cross‐resistance was observed between DMI fungicides difenoconazole and propiconazole, but not between difenoconazole and other fungicide groups, including boscalid, iprodione, or carbendazim. The CYP51gene was 1673 bp encoding 525 amino acids in length and contained two introns. All sensitive and resistant isolates had the identical amino acid sequence of CYP51, with the exception of one resistant isolate carrying a mutation of R511W. A 6 bp insertion in the upstream region was observed in half of the resistant isolates. In the absence of propiconazole, the relative expression of CYP51 was not significantly different in sensitive and resistant isolates. In the presence of difenoconazole, expression of CYP51 gene was induced significantly in the DMI‐resistant isolates but not in the sensitive ones. CONCLUSION: Induced expression of CYP51 in resistant isolates exposed to difenoconazole is an important determinant for DMI resistance in potato pathogens Alternaria sect. © 2019 Society of Chemical Industry

To develop botanical pesticides and repellents against stored-product insects, the chemical composition and insecticide properties of the essential oil from Citrus medica L. var. sarcodactylis Swin...

Objective To investigate the effect of exercise in thermal climates on the renal functions and explore the role of oxidative stress injury in the pathogenesis of exertional heat stroke (EHS). Methods Totally 187 young soldiers in the subtropical area of Southeast China were divided randomly into two groups. All subjects underwent 1.5km, 3km and 5km cross-country running under two different environmental conditions: normal temperature and normal humidity [temperature (26±2) ℃, humidity 50%±5%]; high temperature and high humidity [temperature (33±2) ℃, humidity 65%±5%], and each soldiers' blood samples were taken at pre and post running. The level of Cr, BUN, CK, CK-MB, LDH and SOD were measured by automatic biochemical analyzer. The levels of serum 8-OHdG was detected by enzyme-linked immunosorbent assay (ELISA). Results 1) After exercise, the Cr and BUN of the two groups increased, compared with the pre- exercise the differences were significant (P

The endocrine regulatory roles of the hypothalamic–pituitary–adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa. However, the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone (ACTH), a pro-opiomelanocortin (POMC)-derived peptide, on animal energy expenditure and somatic growth remain unknown. POMC has also been identified as one of the candidate loci for polycystic ovary syndrome, which features hyperandrogenism and some prevalence of obesity in patients. Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models. In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin, which are responsible for their obesity-prone weight gain observed in various pomc mutant mammals, analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish. Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish, with enhanced activation of mammalian target of rapamycin complex 1; reutilization of amino acids and fatty acid β-oxidation are observed in the muscle tissue of the pomca-deficient fish. After reducing hyperandrogenism by crossing our pomca mutant fish with a cyp17a1-deficient background, the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed. Thus, our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates, whereas its effect on adipostasis is unique to teleosts.

Zika virus (ZIKV), a mosquito-borne flavivirus, poses a serious threat to public health worldwide, and Aedes albopictus is one of its vectors. To evaluate the potential of the entomopathogenic fungus Beauveria bassiana for ZIKV vector control, we compared the vectorial capacity of Ae. albopictus females blood-fed with ZIKV with or without exposure to Beauveria bassiana. We found that fungal infection significantly decreased the amount of ZIKV by 3.6-, 12.3- and 7.8-fold in mosquito midguts, heads and salivary glands, respectively. Similarly, fungal infection also reduced the rates of ZIKV dissemination, potential transmission and potential population transmission for mosquitoes by 26.8%, 38.4% and 35.2%, respectively. On the other hand, the median survival time and fecundity of fungus-infected mosquitoes were reduced by 84.2% and 39.8% in comparison with those of the non-fungus-infected mosquitoes. The first gonotrophic cycle length was increased by 15.3% because of fungal infection. This study revealed that B. bassiana infection significantly reduced the vectorial capacity of A. albopictus for ZIKV, which suggested that B. bassiana could be broadly and efficiently used in the field for the control of Zika vectors.

Key points In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown. Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation. Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β-oxidation or autophagy weakened the fasting-induced cold resistance. Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting-induced cold resistance in fish. Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress. Abstract In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild-type or specific gene knock-out zebrafish models (carnitine palmitoyltransferase-1b-deficient strain, CPT1b-/- , or autophagy-related protein 12-deficient strain, ATG12-/- ), we verified that fasting-stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.

The essential oil extracted from roots and rhizomes of Ligusticum jeholense Nakai et Kitagawa was investigated for its chemical composition by GC-MS analysis, and evaluated for its contact toxicity and repellency against Tribolium castaneum and Lasioderma serricorne, along with some of its individual components. The essential oil was rich in aromatics (65.34%) with low molecular weight. Major components included sedanolide (33.95%), 3-butylidenephthalide (18.76%), spathulenol (8.90%) and myristicin (6.76%). The results of bioassays indicated that the essential oil of L. jeholense and 3-butylidenephthalide possessed significant repellent activities against T. castaneum at 2 and 4 h post-exposure. Meanwhile, 3-butylidenephthalide had potent contact toxicity against L. serricorne (LD50 = 13.64 µg/adult). The minor component n-butylbenzene in the oil was highly toxic to T. castaneum (LD50 = 23.99 µg/adult) and L. serricorne (LD50 = 7.86 µg/adult) in contact assays, but failed to repel these beetles at all testing concentrations. Spathulenol and myristicin exerted good insecticidal and repellent effects on the two target insects. This work suggests that the essential oil of L. jeholense has promising potential for development as natural insecticide or repellent to control pest damage in warehouses.

Dietary usage of microencapsulated oils has been proved to promote growth and gut health in land animals, however, these beneficial effects have not been intensively investigated in aquatic animals. The present study hypothesized that dietary microencapsulated oils could alleviate negative effects caused by high-fat diet (HFD) in fish, thus we fed juvenile Nile tilapia with HFD (15% fat) by using normal or microencapsulated oils as lipid sources for 8 weeks. To compare the effects between different microencapsulated oils with different fatty acid composition, two oil mixtures (PL: 60% palm oil +40% linseed oil; FL: 60% fish oil +40% linseed oil) were used. After feeding trial, the growth, body composition, fatty acid composition, resistance to pathogenic bacteria challenge, activities of immune enzymes, expressions of inflammation genes, intestinal structure and microbiota were measured, respectively. The results indicated that microencapsulated oils didn’t affect fish growth, body composition, and muscle fatty acid composition, but improved the intestinal activities of lysozyme (LZM) and resistance against Aeromonas hydrophila. Further tests showed that microencapsulated oils not only improved the structure of intestine, but also increased the number of beneficial bacteria (Bacillus and Paenibacillus) and decreased the number of harmful bacteria (Pseudoalteromonas and Roseovarius) in the intestine. Those beneficial effects are more significant between normal PL oil and microencapsulated PL oil, but no significant difference in FL oil groups. Taken together, these results suggested that microencapsulated oil might enhance immune activities in the Nile tilapia fed with HFD by improving intestinal structure and microflora. Moreover, the beneficial effects of the microencapsulated oil are correlated to the oil composition. To the best of our knowledge, this is the first study illustrating the beneficial effects of dietary microencapsulated oil in the fish fed with HFD.

A new acridone alkaloid, reticarcidone A (1), decorated with an oxygenated isopentenyl group between C-1 and C-2, was isolated from the leaves of

Toxoplasma gondii is an intracellular parasite that infects humans and other warm-blooded animals. Exosomes are endocytic-derived vesicles released by cells, representing an important mode of intercellular communication. In exosomes, specific molecules of proteins, lipids, and mRNAs or miRNAs have been detected, some of which are capable of transferring biologically active molecules to recipient cells. Dendritic cells (DCs) are the only antigen-presenting cells (APCs) that activate the initial immune response. In this study, high-throughput sequencing was used to analyze the exosomal miRNA profile of DC2.4 cells infected with Toxoplasma gondii for 28 h, compared with those of uninfected DC2.4 cells. Differential exosomal miRNAs (DEmiRs) from these two cell groups were analyzed. Through high-throughput sequencing, 3434 DEmiRs were obtained, and 12 stably enriched DEmiRNAs were verified by Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and selected for further analysis. The target genes of these 12 miRNAs were predicted with online analysis software and subjected to bioinformatics analyses including protein&ndash, protein interaction (PPI) network analysis, key driver analysis (KDA), gene ontology (GO) enrichment, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. These DEmiRs were found to be associated with a variety of biological processes and signaling pathways involved in host ubiquitin system, innate immunity, biosynthesis, and transferase activity and could be potential biomarkers for T. gondii infection.

In this study, we detected and genetically characterized rat bocavirus (RBoV) carried in 496 murine rodents that were captured in four provinces in China between May 2015 and May 2017. RBoV-positive samples were found in all four provinces, with a total positive rate of 24.8% (123/496) in throat swabs and 58.1% (286/492) in fecal samples. Twelve nearly full-length genome sequences of RBoV were determined, and the average sequence identity was 96.2%. Phylogenetic analysis showed that RBoVs formed a distinct clade that was distinguishable from the bocaviruses discovered in humans and other animals.

Background Metalaxyl is a phenylamide fungicide, introduced for oomycete management in the 1970s. RPA190 gene has been reported to be associated with metalaxyl resistance, although other genes may also be involved in the process. This study assessed the evolutionary association of amino acid (AA) mutations in RPA190 with metalaxyl resistance in Phytophthora infestans. Results All isolates from Yunnan were resistant to metalaxyl with multiple AA mutations in RPA190. Two main evolutionary pathways were found in metalaxyl resistance: in one pathway, RPA190 from sensitive isolates (SAA) underwent a single type AA mutation at position 1476, changing from valine to glycine (V1476G); the second pathway involved multiple steps of point mutations. In a phylogenetic tree, nucleotide sequences of the gene clustered into six clades largely corresponding to AA isoform groups. Among the clusters, sequences carrying mutations V1476G and P980S formed two independent clades; other clades shared a common mutation of F382Y. All three mutations together with another two were shown to be under positive selection and the number of AA mutations in an isolate was positively correlated with EC50 values. Conclusion Multiple mutations such as V1476G, P980S, and F382Y in RPA190 contribute to metalaxyl resistance, and resistance to metalaxyl can emerge in at least two independent pathways in P. infestans. © 2018 Society of Chemical Industry.

Macrobrachium nipponense is a new aquaculture species with high market demand and is preferred as food by Asian consumers. However, its nutrient requirements and optimal dietary sources have not been fully evaluated. In the present study, we examined four common plant protein sources (soybean meal, cottonseed meal, rapeseed meal, and peanut meal) as partial replacement for 25% fishmeal protein in five isonitrogenous and isocaloric diets in M. nipponense for 8 weeks. The nutritional effects of the four plant protein sources were compared by means of growth performance, feed efficiency, histology, biochemical composition, oxidative stress, total hemocyte count, and in vitro digestion. Prawns fed the diets containing soybean (730.96 ± 33.50%) and cottonseed meals (672.32 ± 74.52%) had higher weight gain than those fed on rapeseed (503.71 ± 50.85%) and peanut (507.79 ± 52.10%) meal diets (p

Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT) have different structures and metabolic functions and play different roles in the regulation of the mammal endocrine system. However, little is known about morphology and physiological and metabolic functions between VAT and SCAT in fish. We compared the morphological, physiological, and biochemical characteristics of VAT and SCAT in Nile tilapia and measured their functions in energy intake flux, lipolytic ability, and gene expression patterns. SCAT contained more large adipocytes and nonadipocytes than VAT in Nile tilapia. VAT had higher lipid content and was the primary site for lipid deposition. Conversely, SCAT had higher hormone-induced lipolytic activity. Furthermore, SCAT had a higher percentage of monounsaturated and lower polyunsaturated fatty acids than VAT. SCAT had higher mitochondrial DNA, gene expression for fatty acid β-oxidation, adipogenesis, and brown adipose tissue characteristics, but it also had a lower gene expression for inflammation and adipocyte differentiation than VAT. SCAT and VAT have different morphological structures, as well as physiological and metabolic functions in fish. VAT is the preferable lipid deposition tissue, whereas SCAT exhibits higher lipid catabolic activity than VAT. The physiological functions of SCAT in fish are commonly overlooked. The present study indicates that SCAT has specific metabolic characteristics that differ from VAT. The differences between VAT and SCAT should be considered in future metabolism studies using fish as models, either in biomedical or aquaculture studies.

Nutritional values of animal diets depend on the type of oil in the feed ingredient, but the underlying metabolic mechanisms of dietary oil in animal feed have not been thoroughly studied in aquatic animals, especially in crustaceans. In the present study, we conducted assays on GC–MS-based metabolomics and nutritional parameters to investigate the metabolic mechanisms between juvenile Chinese mitten crabs ( Eriocheir sinensis ) fed olive oil containing 69% oleic acid (OA) and perilla oil containing 56% linolenic acid (LNA). Crab fed OA displayed faster growth, lower concentrations of hepatic glycogen, triglycerides and peroxidation products than those fed LNA. In the metabolomics assay, among 222 peaks isolated, 69 peaks were identified in serum. Among 13 significantly different metabolites between OA and LNA groups, six metabolites related to glycolysis and TCA (tricarboxylic acid) cycle (pyruvate, succinic acid, lactose, malic acid, D-glyceric acid and threitol), methionine, 2-keto-isovaleric acid (intermediate for valine and leucine synthesis) and 2-hydroxybutanoic acid (intermediate for glutathione synthesis) were higher in the OA group than in the LNA group. Only glutaconic acid (intermediate of ketogenic amino acids breakdown) was higher in the LNA group. This study indicates that crab in the OA group increased degradation of glucose and lipids to provide energy for growth as compared with crab in the LNA group. This is the first metabolomics study to identify the key pathways and crucial metabolites as biomarkers to differentiate the metabolic mechanisms of crustaceans fed contrasting dietary oils.

The spread of antimicrobial resistance and global change in air temperature represent two major phenomena that are exerting a disastrous impact on natural and social issues but investigation of the interaction between these phenomena in an evolutionary context is limited. In this study, a statistical genetic approach was used to investigate the evolution of antimicrobial resistance in agricultural ecosystem and its association with local air temperature, precipitation and UV radiation. We found no resistance to mancozeb, a non-specific fungicide widely used in agriculture for more than half a century, in 215 Alternaria alternata isolates sampled from geographic locations along a climatic gradient and cropping system representing diverse ecotypes in China, consistent with low resistance risk in many non-specific fungicides. Genetic variance accounts for ~35% of phenotypic variation while genotype-environment interaction is negligible, suggesting that heritability plays a more important role in the evolution of resistance to mancozeb in plant pathogens than phenotypic plasticity. We also found that tolerance to mancozeb in agricultural ecosystem is under constraining selection and significantly associated with local air temperature, possibly resulting from a pleiotropic effect of resistance with thermal and other ecological adaptations. The implication of these results for fungicide and other antimicrobial management in the context of global warming is discussed. This article is protected by copyright. All rights reserved.

Energy metabolism plays important roles in stress resistance and immunity in mammals, however, such functions have not been established in fish. In the present study, Nile tilapia (Oreochromis niloticus) was fed with mildronate, an inhibitor of mitochondrial fatty acid (FA) β-oxidation, for six weeks subsequently challenged with Aeromonas hydrophila and ammonia nitrogen exposure. Mildronate treatment reduced significantly l-carnitine concentration and mitochondrial FA β-oxidation efficiency, while it increased lipid accumulation in liver. The fish with inhibited hepatic FA catabolism had lower survival rate when exposed to Aeromonas hydrophila and ammonia nitrogen. Moreover, fish fed mildronate supplemented diet had lower immune enzymes activities and anti-inflammatory cytokine genes expressions, but had higher pro-inflammatory cytokine genes expressions. However, the oxidative stress-related biochemical indexes were not significantly affected by mildronate treatment. Taken together, inhibited mitochondrial FA β-oxidation impaired stress resistance ability in Nile tilapia mainly through inhibiting immune functions and triggering inflammation. This is the first study showing the regulatory effects of lipid catabolism on stress resistance and immune functions in fish.

1α,25(OH)2D3 (vitamin D3) is crucial for mineral homeostasis in mammals, but the precise effects of 1α,25(OH)2D3 in adipose tissue remain to be clarified in vivo. The initial 25-hydroxylation is catalyzed by liver microsomal cytochrome P450 2R1 (CYP2R1), which is conserved in vertebrates. To probe the physiological function(s) of 1α,25(OH)2D3 in teleosts, we generated two independent cyp2r1-deficient zebrafish lines. These mutants exhibit retarded growth and increased obesity, especially in the visceral adipose tissue (VAT). These defects could be rescued with 25(OH)D3 treatments. ChIP-PCR analyses demonstrated that pgc1a is the target of the vitamin D receptor in the liver and VAT of zebrafish. Significantly decreased protein levels of Pgc1a, impaired mitochondrial biogenesis, and free fatty acid oxidation are also observed in the cyp2r1 mutant VAT. Our results demonstrate that regulation of 1α,25(OH)2D3 during lipid metabolism occurs through the regulation of Pgc1a for mitochondrial biogenesis and oxidative metabolism within zebrafish VAT.