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This study aimed to investigate the temporal dynamics of physiological and gut microbial responses in Mule ducks (M-D) during force-feeding (F-F), with the goal of identifying potential regulatory targets to reduce feeding stress. Male M-Ds were subjected to either F-F or ad libitum feeding. We conducted longitudinal analysis at 72, 78, and 84 days of age to assess growth performance, serum biochemical profiles, and intestinal inflammatory markers, while assessing gut microbiota composition through 16S rDNA sequencing. The F-F group exhibited superior growth performance. Initial physiological responses at day 72 included significantly reduced serum corticotropin-releasing hormone (CRH) and jejunal tumor necrosis factor-alpha (TNF−α). Conversely, F-F induced a persistent and profound alteration in the gut microbiome by day 84, characterized by reduced alpha diversity and a significant enrichment of the genus Limosilactobacillus. Correlation analysis identified Limosilactobacillus as a keystone taxon, strongly associated with intestinal metabolites. Our findings demonstrate that M-Ds undergo time-dependent metabolic and immunological adaptations in response to F-F stress, which correlates with distinct alterations in gut microbiota composition, particularly the enrichment of Limosilactobacillus. These findings provide a theoretical basis for developing microbiota-targeted strategies to alleviate F-F stress in foie gras production.

We aimed to explore the influence of different force-feeding intensities on foie gras performance. Geese were force-fed with A (force-feeding four times per day and lasting 28 days) and B (force-feeding 5 times per day and lasting 18 days) at two levels of force-feeding intensities in this study. An integrative analysis of the liver transcriptome, amino acid metabolome, and long-chain fatty acid metabolome was performed. In serum, the levels of blood glucose, insulin, triglyceride (TG), and very low-density lipoprotein (VLDL) of the B group were significantly higher than those of the A group ( p  < 0.05). The B force-feeding intensity induced more severe steatosis in the goose liver. Transcriptome analysis showed that 948 upregulated differentially expressed genes (DEGs) and 519 downregulated DEGs were identified (A vs. B); key DEGs G6PD , IGF1 , IGF2 , and MLX were upregulated; LPL , IRS1 , IRS4 , and IGF1R were downregulated. Principal component analysis (PCA) indicated that there was clear separation and discrimination in liver free amino acids profiles and long-chain fatty acids profiles between the A and B groups, respectively. The Lys level of the B group was significantly higher than that of the A group ( p  < 0.05). The highest enrichment pathway of different amino acids was valine, leucine, and isoleucine biosynthesis, whereas alanine, aspartate, and glutamate metabolism was the pathway involved with the highest impact score. The levels of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), unsaturated fatty acids (UFAs), C14:0, C16:1, C16:0, C18:2n6c, C18:1n9c, and C18:0 of the B group were significantly higher than those of the A group ( p  < 0.05). The highest impact score pathway related to different fatty acids was linoleic acid metabolism, and the highest enrichment pathway involved in different fatty acids was biosynthesis of unsaturated fatty acids. In conclusion, liver DEGs involved in glucolipid metabolism, different free amino acids, and different fatty acids collectively shaped the foie gras performance difference induced by different force-feeding intensities.

Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (10 7 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 10 6  CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log 10 CFU/larvae, while antibiotic treatment led to a 3 log 10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models.

Replacement of fishmeal in feeds is critical for sustainable aquaculture growth. However, replacement with plant protein concentrates reduces fish performance. A rainbow trout strain selected for high performance on a plant protein diet was compared to a non-selected strain to identify physiological mechanisms associated with improved performance. Nutrient digestibility in fishmeal and plant protein diets was assessed and no strain differences were found. Levels of amino acids in the hepatic portal vein and caudal vein were measured at intervals after a single force-feeding of fishmeal, four plant protein concentrates, and a mixture of the concentrates with or without supplementation of three limiting amino acids. Each ingredient affected plasma amino acid levels in a singular manner when fed individually but without predictable additive effects when fed as a mixture. Amino acid supplementation altered uptake and plasma concentrations of all the essential amino acids. The selected trout strain fed the plant protein mixture with amino acids showed a synchronous and homogenous pattern for essential amino acids over time in the hepatic portal vein in contrast to that of the non-selected strain. The results demonstrate that selection favorably altered temporal dynamics of plant protein digestion.

Child eating and caregiver feeding behaviours are critical determinants of food intake, but they are poorly characterized in undernourished children. We aimed to describe how appetite, food refusal and force‐feeding vary between undernourished and healthy children aged 6–24 months in Nairobi and identify potential variables for use in a child eating behaviour scale for international use. This cross‐sectional study was conducted in seven clinics in low‐income areas of Nairobi. Healthy and undernourished children were quota sampled to recruit equal numbers of undernourished children (weight for age [WAZ] or weight for length [WLZ] Z scores ≤2SD) and healthy children (WAZ > 2SD). Using a structured interview schedule, questions reflecting child appetite, food refusal and caregiver feeding behaviours were rated using a 5‐point scale. Food refusal and force‐feeding variables were then combined to form scores and categorized into low, medium and high. In total, 407 child–caregiver pairs, aged median [interquartile range] 9.98 months [8.7 to 14.1], were recruited of whom 55% were undernourished. Undernourished children were less likely to ‘love food’ (undernourished 78%; healthy 90% p = < 0.001) and more likely to have high food refusal (18% vs. 3.3% p = <0.001), while their caregivers were more likely to use high force‐feeding (28% vs. 16% p = 0.03). Undernourished children in low‐income areas in Nairobi are harder to feed than healthy children, and force‐feeding is used widely. A range of discriminating variables could be used to measure child eating behaviour and assess the impact of interventions.

To study the effect of Dapagliflozin on ferroptosis in rabbits with chronic heart failure and to reveal its possible mechanism. Nine healthy adult male New Zealand white rabbits were randomly divided into Sham group (only thorax opening was performed in Sham group, no ascending aorta circumferential ligation was performed), Heart failure group (HF group, ascending aorta circumferential ligation was performed in HF group to establish the animal model of heart failure), and Dapagliflozin group (DAPA group, after the rabbit chronic heart failure model was successfully made in DAPA group). Dapagliflozin was given by force-feeding method. Echocardiography was used to assess cardiac function, HE staining to evaluate pathological changes in the heart, Prussia blue staining to observe iron ions in myocardial tissue, and enzyme-linked immunosorbent assay (ELISA) to determine serum levels of the inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) at the end of week 12 and/or the end of week 16. The oxidative stress related indexes of malondialdehyde (MDA), superoxide dismutase (SOD) and superoxide dismutase (GSH-Px) in serum were quantitatively analyzed by colorimetry. Protein expression levels of nuclear factor E2-related factor 2(Nrf2), heme oxygenase-1(HO-1), glutathione peroxidase 4(Gpx4) were detected by Western blot. In animals with chronic heart failure, Dapagliflozin improved cardiomyocyte hypertrophy, degeneration and necrosis. Dapagliflozin increased serum GSH-Px and SOD levels and decreased IL-1β, IL-6, TNF-α and MDA levels (P < 0.05) in a rabbit model of heart failure. Dapagliflozin also decreased cardiac iron ion levels and increased Nrf2, HO-1 and GPX4 protein expression. Dapagliflozin can improve heart failure by inhibiting oxidative stress and ferroptosis, and its mechanism may be related to the regulation of Nrf2/HO-1/GPX4 signaling pathway.

We assessed the impact of the Janus Kinase (JAK) 1 inhibitor itacitinib on xenogeneic graft-versus-host disease (xGVHD). XGVHD was induced by i.v. injection 20 × 106 human peripheral blood mononuclear cells (hPBMC) in NSG mice on day 0. Itacitinib (3 mg, ≈120 mg/kg) or methylcellulose was administered by force-feeding twice a day from day 3 to day 28. Mice were followed for xGVHD score and survival. In addition, human T-cell engraftment and as well as human T-cell subtypes were monitored in blood on days 14, 21, and 28 after transplantation. We observed that itacitinib-treated mice had significantly longer survival than control mice (median 45 versus 33 days; P < 0.001). Further, they also had lower absolute numbers of human CD4+ T cells on days 21 and 28 after transplantation as well as of human CD8+ T cells on days 14, 21, and 28 after transplantation. In addition, itacitinib-treated mice had higher frequencies of human regulatory T cells (Treg) on days 21 and 28 after transplantation. In summary, our data indicate that itacitinib decreases human T-cell engraftment, increases Treg frequencies and attenuates xGVHD in NSG mice transplanted with hPBMC.

The polyether toxin, okadaic acid, causes diarrhetic shellfish poisoning in humans. Despite extensive research into its cellular targets using rodent models, we know little about its putative effect(s) on innate immunity. We inoculated larvae of the greater wax moth, Galleria mellonella, with physiologically relevant doses of okadaic acid by direct injection into the haemocoel (body cavity) and/or gavage (force-feeding). We monitored larval survival and employed a range of cellular and biochemical assays to assess the potential harmful effects of okadaic acid. Okadaic acid at concentrations ≥ 75 ng/larva (≥ 242 μg/kg) led to significant reductions in larval survival (> 65%) and circulating haemocyte (blood cell) numbers (> 50%) within 24 h post-inoculation. In the haemolymph, okadaic acid reduced haemocyte viability and increased phenoloxidase activities. In the midgut, okadaic acid induced oxidative damage as determined by increases in superoxide dismutase activity and levels of malondialdehyde (i.e. lipid peroxidation). Our observations of insect larvae correspond broadly to data published using rodent models of shellfish-poisoning toxidrome, including complementary LD50 values: 206–242 μg/kg in mice, ~ 239 μg/kg in G. mellonella. These data support the use of this insect as a surrogate model for the investigation of marine toxins, which offers distinct ethical and financial incentives.

Indomethacin is a non-steroidal anti-inflammatory drug that causes gastric ulceration and increased ‘leakiness’ in rat models, and is used routinely as a toxicology assay to screen novel compounds for repair and restitution properties. We set out to establish conditions for indomethacin-induced gut damage in wax-moth (Galleria mellonella) larvae with a view to reducing the need for rodents in such experimentation. We administered indomethacin (0.5–7.5 µg/larva; 2–30 mg/kg) to G. mellonella via intrahaemocoelic injection and gavage (force-feeding) and monitored survival and development, blood cell (haemocyte) numbers, and changes in gut permeability. Increased levels of gut leakiness were observed within the first 4- to 24 h by tracking fluorescent microspheres in the faeces and haemolymph (blood equivalent). Additionally, we recorded varying levels of tissue damage in histological sections of the insect midgut, including epithelial sloughing and cell necrosis. Degeneration of the midgut was accompanied by significant increases in detoxification-associated activities (superoxide dismutase and glutathione-S-transferase). Herein, we present the first evidence that G. mellonella larvae force-fed indomethacin display broad symptoms of gastric damage similar to their rodent counterparts.

Mule ducks have been force-fed to develop a hepatic steatosis, also called “foie gras”, which is similar to the non-alcoholic fatty liver disease (NAFLD) described in humans and mammals. However, in hepatic steatosis resulting from force-feeding of ducks, very little is known about the fine biochemical events that occur due to the enormous and very rapid increase in total lipids that mainly accumulate in hepatocytes. To begin to reduce this lack of knowledge associated with the development of this specific hepatic steatosis, liver samples were taken at different times to follow the overall biochemical transformation of the liver as well as different markers of oxidative stress, hypoxia and apoptosis. The results indicate that the lipid content increases rapidly in the liver throughout the force-feeding period while the protein content decreases. The amount of hydroxyproline remains constant indicating that no liver fibrosis develops during the force-feeding period. On the contrary, all the tested biomarkers of cellular oxidative stress increase rapidly but without any visible disorder in the coordination of paired activities. At the same time, hypoxia-inducible factors also increase indicating that a hypoxia situation is gradually occurring in hepatocytes. This leads, in addition to the lipotoxicity induced by the accumulation of lipids, to an increased number of liver cells to enter into apoptosis. A relative variability in the level of these cellular responses was also observed indicating that, probably, certain animals support the development of this steatosis differently. This leads us to imagine that the physiological status of these birds may differ widely for reasons that remain to be clarified.