The interaction of ER stress and autophagy in trophoblasts: navigating pregnancy outcome.

The endoplasmic reticulum (ER) is a complex and dynamic organelle that initiates unfolded protein response (UPR) and endoplasmic reticulum stress (ER Stress) in response to the accumulation of unfolded or misfolded proteins within its lumen. Autophagy is a paramount intracellular degradation system that facilitates the transportation of proteins, cytoplasmic components, and organelles to lysosomes for degradation and recycling. Preeclampsia (PE) and intrauterine growth retardation (IUGR) are two common complications of pregnancy associated with abnormal trophoblast differentiation and placental dysfunctions and have a major impact on fetal development and maternal health. The intricate interplay between ER Stress, and autophagy and their impact on pregnancy outcomes, through mediating trophoblast differentiation and placental development, has been highlighted in various reports. Autophagy controls trophoblast regulation through a variety of gene expressions and signalling pathways while excessive ER Stress triggers downstream apoptotic signalling, culminating in trophoblast apoptosis. This comprehensive review delves into the intricacies of placental development and explores the underlying mechanisms of PE and IUGR. In addition, this review will elucidate the molecular mechanisms of ER Stress and autophagy, both individually and in their interplay, in mediating placental development and trophoblast differentiation, particularly highlighting their roles in PE and IUGR development. This research seeks to the interplay between ER Stress and impaired autophagy in the placental trophoderm, offering novel insights into their contribution to pregnancy complications.

Recent progress in optical and electrochemical aptasensor technologies for detection of aflatoxin B1.

AFB1 (Aflatoxin B1) contamination is becoming a global concern issue due to its extraordinary occurrence, severe toxicity, as well as the great influence on the economic losses, food safety and environment. Therefore, it is desirable to develop novel analytical techniques for simple, rapid, accurate, and even point-of-care testing of AFB1. Fortunately, aptamer, considered as a new generation bioreceptor and even superior to classic antibody and enzyme, has been emerged remarkable application in food hazards detection. Correspondingly, aptasensors have been well-established toward AFB1 determination with outstanding performance. In this article, we first discuss and summarize the recent progress in optical and electrochemical aptasensors to monitor AFB1 over the past three years. In particular, the embedding of advanced nanomaterials for their improved analytical performance is highlighted. Furthermore, the critical analysis on various signal transduction strategies for aptasensors construction is discussed. Finally, we reveal the challenges and provide our opinion in future opportunities for aptasensor development.

Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light-dark cycles: A multiomics study.

The accelerated pace of life at present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light-dark (LD) cycles will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host-microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multiomics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, and Clostridia vadinBB60 et al. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM-liver-brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers.

A coalitional game-based joint monitoring mechanism for combating COVID-19.

In the absence of effective treatment for COVID-19, disease prevention and control have become a top priority across the world. However, the general lack of effective cooperation between communities makes it difficult to suppress the community spread of the global pandemic; hence repeated outbreaks of COVID-19 have become the norm. To address this problem, this paper considers community cooperation in disease monitoring and designs a joint epidemic monitoring mechanism, in which adjacent communities cooperate to enhance their monitoring capability. In this work, we formulate the epidemiological monitoring process as a coalitional game. Then, we propose a Shapley value-based payoffs distribution scheme for the coalitional game. A comprehensive analytical framework is developed to evaluate the advantages and sustainability of the cooperation between communities. Experimental results show that the proposed mechanism performs much better than the conventional non-cooperative monitoring design and can greatly increase each community's payoffs.

Effects of the maternal gut microbiome and gut-placental axis on melatonin efficacy in alleviating cadmium-induced fetal growth restriction.

Cadmium (Cd) is a major environmental stressor that induces fetal growth restriction (FGR). Also, changes in gut microbiome diversity-which can be modulated positively by melatonin (Mel) have implications on fetal development and placental functions. Therefore, this study aimed to explore whether the role of Mel in counteracting the Cd-induced FGR by regulating placental barrier injury, endoplasmic reticulum stress (ERS) and mitophagy in pregnant mice is mediated-in part- via the gut microbiota modulations. Pregnant mice were intraperitoneally injected with CdCl2 (5 mg/kg) and Mel (5 mg/kg) once daily, respectively, at the same time from gestational day (GD) 8 to GD18, and then the maternal colon and placental tissues were collected for detection. To investigate the inner relationship between intestinal flora and the protection of Mel on FGR caused by Cd, gut microbiota transplantation (GMT) was carried out from GD0 to GD18 after the removal of intestinal microbiota by antibiotics. Results indicated that Mel relieved barrier injury, ERS and mitophagy in the placenta, and reversed the maternal gut microbiota dysbiosis. The GMT approach suggested a role of intestinal microbiota in placental barrier injury, ERS and mitophagy induced by Cd. Overall, the results highlighted that the intestinal microbiota and gut-placental axis play a central role in the protective effect of Mel against Cd-induced FGR.

The Short-Day Cycle Induces Intestinal Epithelial Purine Metabolism Imbalance and Hepatic Disfunctions in Antibiotic-Mediated Gut Microbiota Perturbation Mice.

Intestinal microbiota dysbiosis is related to many metabolic diseases in human health. Meanwhile, as an irregular environmental light-dark (LD) cycle, short day (SD) may induce host circadian rhythm disturbances and worsen the risks of gut dysbiosis. Herein, we investigated how LD cycles regulate intestinal metabolism upon the destruction of gut microbes with antibiotic treatments. The growth indices, serum parameters, concentrations of short-chain fatty acids (SCFAs), and relative abundance of intestinal microbes were measured after euthanasia; intestinal contents, epithelial metabolomics, and hepatic transcriptome sequencing were also assessed. Compared with a normal LD cycle (NLD), SD increased the body weight, spleen weight, and serum concentration of aspartate aminotransferase, while it decreased high-density lipoprotein. Meanwhile, SD increased the relative abundance of the Bacteroidetes phylum while it decreased the Firmicutes phylum in the gut of ABX mice, thus leading to a disorder of SCFA metabolism. Metabolomics data revealed that SD exposure altered gut microbial metabolism in ABX mice, which also displayed more serious alterations in the gut epithelium. In addition, most differentially expressed metabolites were decreased, especially the purine metabolism pathway in epithelial tissue. This response was mainly due to the down-regulation of adenine, inosine, deoxyguanosine, adenylsuccinic acid, hypoxanthine, GDP, IMP, GMP, and AMP. Finally, the transcriptome data also indicated that SD has some negative effects on hepatic metabolism and endocrine, digestive, and disease processes. Overall, SD induced an epithelial and hepatic purine metabolism pathway imbalance in ABX mice, as well as the gut microbes and their metabolites, all of which could contribute to host metabolism and digestion, endocrine system disorders, and may even cause diseases in the host.

l-Arginine Inhibits Apoptosis of Ovine Intestinal Epithelial Cells through the l-Arginine-Nitric Oxide Pathway.

BACKGROUND: In nonruminants, many of the biological roles of l-arginine (Arg) at the intestinal level are mediated through the Arg-nitric oxide (Arg-NO) pathway. Whether the Arg-NO pathway is involved in controlling the immune response and viability in ovine intestinal epithelial cells (IOECs) is unclear. OBJECTIVES: The current study aimed to examine the role of the Arg-NO pathway in apoptosis, antioxidant capacity, and mitochondrial function of IOECs. METHODS: The IOECs were incubated in Arg-free DMEM supplemented with 150 µM Arg (CON) or 300 µM Arg (ARG) alone or with 350 µM Nw-nitro-l-arginine methyl ester hydrochloride (l-NAME) (CON + NAME, ARG + NAME) for 24 h. The reactive oxygen species (ROS) concentration, antioxidant capacity, and cell apoptotic percentage were determined. RESULTS: Arg supplementation decreased (P < 0.05) the ROS concentration (38.9% and 22.7%) and apoptotic cell percentage (57.2% and 54.8%) relative to the CON and CON + NAME groups, respectively. Relative to the CON and ARG treatments, the l-NAME administration decreased (P < 0.05) the mRNA abundance of superoxide dismutase 2 (32% and 21.3%, respectively) and epithelial NO synthase (36% and 29.1%, respectively). Arg supplementation decreased (P < 0.05) the protein abundance of apoptosis antigen 1 (FAS) (52.0% and 43.9%) but increased (P < 0.05) those of nuclear respiratory factor 1 (31.3% and 22.9%) and inducible NO synthase (35.2% and 41.8%) relative to the CON and CON + NAME groups, respectively. CONCLUSIONS: The inhibition of apoptosis in IOECs due to the increased supply of Arg is associated with the mitochondria- and FAS-dependent pathways through the activity of the Arg-NO pathway. The findings help elucidate the role of the Arg-NO pathway in IOEC growth and apoptosis.

Dietary Supplementation of L-Arginine and N-Carbamylglutamate Attenuated the Hepatic Inflammatory Response and Apoptosis in Suckling Lambs with Intrauterine Growth Retardation.

L-arginine (Arg) is a semiessential amino acid with several physiological functions. N-Carbamylglutamate (NCG) can promote the synthesis of endogenous Arg in mammals. However, the roles of Arg or NCG on hepatic inflammation and apoptosis in suckling lambs suffering from intrauterine growth restriction (IUGR) are still unclear. The current work is aimed at examining the effects of dietary Arg and NCG on inflammatory and hepatocyte apoptosis in IUGR suckling lambs. On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 432 twin lambs. Normal-birthweight and IUGR Hu lambs were allocated randomly (n = 12/group) to control (CON), IUGR, IUGR+1% Arg, or IUGR+0.1% NCG groups. Lambs were fed for 21 days from 7 to 28 days old. Compared with CON lambs, relative protein 53 (P53), apoptosis antigen 1 (Fas), Bcl-2-associated X protein (Bax), caspase-3, cytochrome C, tumor necrosis factor alpha (TNF-α), nuclear factor kappa-B (NF-κB) p65, and NF-κB pp65 protein levels were higher (P < 0.05) in liver from IUGR lambs, whereas those in liver from IUGR lambs under Arg or NCG treatment were lower than those in IUGR lambs. These findings indicated that supplementing Arg or NCG reduced the contents of proinflammatory cytokines at the same time when the apoptosis-related pathway was being suppressed, thus suppressing the IUGR-induced apoptosis of hepatic cells.

Ruminal epithelial cell proliferation and short-chain fatty acid transporters in vitro are associated with abundance of period circadian regulator 2 (PER2).

The major circadian clock gene PER2 is closely related to cell proliferation and lipid metabolism in various nonruminant cell types. Objectives of the study were to evaluate circadian clock-related mRNA abundance in cultured goat ruminal epithelial cells (REC), and to determine effects of PER2 on cell proliferation and mRNA abundance of short-chain fatty acid (SCFA) transporters, genes associated with lipid metabolism, cell proliferation, and apoptosis. Ruminal epithelial cells were isolated from weaned Boer goats (n = 3; 2 mo old; ∼10 kg of body weight) by serial trypsin digestion and cultured at 37°C for 24 h. Abundance of CLOCK and PER2 proteins in cells was determined by immunofluorescence. The role of PER2 was assessed through the use of a knockout model with short interfering RNA, and sodium butyrate (15 mM) was used to assess the effect of upregulating PER2. Both CLOCK and PER2 were expressed in REC in vitro. Sodium butyrate stimulation increased mRNA and protein abundance of PER2 and PER3. Furthermore, PER2 gene silencing enhanced cell proliferation and reduced cellular apoptosis in isolated REC. In contrast, PER2 overexpression in response to sodium butyrate led to lower cellular proliferation and ratio of cells in the S phase along with greater ratio of cells in the G2/M phase. Those responses were accompanied by downregulated mRNA abundance of CCND1, CCNB1, CDK1, and CDK2. Among the SCFA transporters, PER2 silencing upregulated mRNA abundance of MCT1 and MCT4. However, it downregulated mRNA abundance of PPARA and PPARG. Overexpression of PER2 resulted in lower mRNA abundance of MCT1 and MCT4, and greater PPARA abundance. Overall, data suggest that CLOCK and PER2 might play a role in the control of cell proliferation, SCFA, and lipid metabolism. Further studies should be conducted to evaluate potential mechanistic relationships between circadian clock and SCFA absorption in vivo.

N-Carbamylglutamate and l-Arginine Promote Intestinal Absorption of Amino Acids by Regulating the mTOR Signaling Pathway and Amino Acid and Peptide Transporters in Suckling Lambs with Intrauterine Growth Restriction.

BACKGROUND: Previous studies have revealed that dietary N-carbamylglutamate (NCG) and l-arginine (Arg) improve intestinal integrity, oxidative state, and immune function in Hu suckling lambs with intrauterine growth restriction (IUGR). Whether these treatments alter intestinal nutrient absorption is unknown. OBJECTIVE: The aim of this study was to determine the influence of dietary NCG and Arg treatment during the suckling period on intestinal amino acid (AA) absorption, alterations in the mechanistic target of rapamycin (mTOR) signaling pathway, and the abundance of AA and peptide transporters in IUGR lambs. METHODS: On day 7 after birth, 48 newborn Hu lambs were selected from a cohort of 424 twin lambs. Normal-birth-weight and IUGR Hu lambs were allocated randomly (n = 12/group) to a control (4.09 ± 0.12 kg), IUGR (3.52 ± 0.09 kg), IUGR + 0.1% NCG (3.49 ± 0.11 kg), or IUGR + 1% Arg (3.53 ± 0.10 kg). RESULTS: At day 28, compared with the IUGR group, the IUGR groups receiving NCG and Arg had 7.4% and 7.2% greater (P < 0.05) body weight, respectively. Compared with the IUGR group, the serum concentration of insulin was greater (P < 0.05) and the cortisol was lower (P < 0.05) in the IUGR groups receiving NCG and Arg. Compared with the IUGR group, the IUGR groups receiving NCG and Arg had 13.2%-62.6% greater (P < 0.05) serum concentrations of arginine, cysteine, isoleucine, and proline. Dietary NCG or Arg to IUGR lambs resulted in greater protein abundance (P < 0.05) of peptide transporter 1 (41.9% or 38.2%) in the ileum compared with the unsupplemented IUGR lambs, respectively. Furthermore, dietary NCG or Arg treatment normalized the IUGR-induced variation (P < 0.05) in the ileal ratio of phosphorylated mTOR to total mTOR protein. CONCLUSION: Both NCG and Arg can help mitigate the negative effect of IUGR on nutrient absorption in neonatal lambs.

Effects of different dietary ratio of metabolizable glucose and metabolizable protein on growth performance, rumen fermentation, blood biochemical indices and ruminal microbiota of 8 to 10-month-old dairy heifers.

OBJECTIVE: The aim of this experiment was to evaluate the effects of different dietary ratio of metabolizable glucose (MG) to metabolizable protein (MP) on growth performance, blood metabolites, rumen fermentation parameters and the ruminal microbial community of 8 to 10-month-old heifers. METHODS: A total of 24 Holstein heifers weighing an average of 282.90 kg (8 month of age) were randomly assigned to four groups of six. The heifers were fed one of four diets of different dietary MG/MP (0.97, 1.07, 1.13, and 1.26). RESULTS: The results showed that the ratio of MG/MP affected the growth performance, blood metabolites, rumen fermentation parameters and the ruminal microbial community of heifers. The average daily gain of heifers was enhanced by increasing the ratio of MG/MP (p<0.05). The concentration of blood urea nitrogen, cholesterol, and low density lipoprotein cholesterol as well as the concentration of total volatile fatty acid in the rumen fluid of heifers decreased with the improvement in the ratio of dietary MG/MP (p<0.05). However, the relative amount of Ruminococcus albus and Butyrivibrio fibrisolvens in the rumen of heifers was increased significantly (p<0.05) when the dietary MG/MP increased. At the same time, with the improvement in dietary MG/MP, the amount of Fibrobacter succinogenes increased (p = 0.08). CONCLUSION: A diet with an optimal ratio (1.13) of MG/MP was beneficial for the improvement of growth, rumen fermentation, dietary protein and energy utilization of 8 to 10-month-old dairy heifers in this experiment.

Effects of different dietary ratio of physically effective neutral detergent fiber and metabolizable glucose on rumen fermentation, blood metabolites and growth performance of 8 to 10-month-old heifers.

OBJECTIVE: The present study was undertaken to determine an optimal balance between the amount of physically effective neutral detergent fiber (peNDF) to metabolizable glucose (MG) on rumen fermentation, blood metabolites and growth performance of 8 to 10-month-old heifers. METHODS: A total of 15 healthy Holstein heifers weighing an average of 256 kg (8 month of age) were randomly assigned to three groups of five. Treatment diets consisted of the following three peNDF8.0/MG levels: 1.46 (Treatment A), 1.74 (Treatment B), and 2.08 (Treatment C). RESULTS: The results showed that the ratio of peNDF8.0/MG affected rumen fermentation, blood metabolites and growth performance of heifers. The average daily gain of heifers tended to decrease as the ratio of peNDF8.0/MG increased (p = 0.07). The concentrations of blood urea nitrogen, triglyceride, and cholesterol increased significantly (p<0.05), while the high-density lipoprotein concentration decreased (p<0.05). After feeding 2 h and 4 h, insulin concentration in Treatment A was greater than Treatment C (p<0.05). Propionate concentration had decreasing trend (p = 0.07); acetate to propionate ratio and non-glucogenic to glucogenic volatile fatty acid (NGR) increased significantly (p<0.05). In addition, the digestibility of dry matter, crude protein, neutral detergent fiber, and acid detergent fiber decreased significantly (p<0.05). CONCLUSION: The present investigation indicated that dietary peNDF8.0/MG ratio can affect the growth and development, blood metabolites, rumen fermentation and apparent digestibility of heifers, and the optimal dietary peNDF8.0/MG ratio for 8 to 10-month-old heifers in the present study was 1.46.

Effects of Glucose and Starch on Lactate Production by Newly Isolated Streptococcus bovis S1 from Saanen Goats.

UNLABELLED: When ruminants are fed high-concentrate diets, Streptococcus bovis proliferates rapidly and produces lactate, potentially causing rumen acidosis. Understanding the regulatory mechanisms of the metabolism of this species might help in developing dietary strategies to alleviate rumen acidosis. S. bovis strain S1 was newly isolated from the ruminal fluid of Saanen dairy goats and then used to examine the effects of glucose and starch on bacterial metabolism and gene regulation of the organic acid-producing pathway in cultures at a pH of 6.5. Glucose or starch was added to the culture medium at 1 g/liter, 3 g/liter (close to a normal range in the rumen fluid), or 9 g/liter (excessive level). Lactate was the dominant acid produced during the fermentation, and levels increased with the amount of glucose or starch in a dose-dependent manner (P < 0.001). The production of formate and acetate in the fermentation media fluctuated slightly with the dose but accounted for small fractions of the total acids. The activities of lactate dehydrogenase (LDH) and α-amylase (α-AMY) increased with the starch dose (P < 0.05), but the α-AMY activity did not change with the glucose dose. The relative expression levels of the genes ldh, pfl (encoding pyruvate formate lyase), ccpA (encoding catabolite control protein A), and α-amy were higher at a dose of 9 g/liter than at 1 g/liter (P < 0.05). Expression levels of pfl and α-amy genes were higher at 3 g/liter than at 1 g/liter (P < 0.05). The fructose 1,6-diphosphate (FDP) concentration tended to increase with the glucose and starch concentrations. In addition, the S. bovis S1 isolate fermented glucose much faster than starch. We conclude that the quantities of glucose and soluble starch had a major effect on lactate production due to the transcriptional regulation of metabolic genes. IMPORTANCE: This work used a newly isolated S. bovis strain S1 from the rumen fluid of Saanen goats and examined the effects of glucose and soluble starch on organic acid patterns, enzyme activity, and expression of genes for in vitro fermentation. It was found that lactate was the dominant product from S. bovis strain S1, and the quantities of both glucose and starch in the medium were highly correlated with lactate production and with the corresponding changes in associated enzymes and genes. Therefore, manipulating the metabolic pathway of S. bovis to alter the dietary level of readily fermentable sugar and carbohydrates may be a strategy to alleviate rumen acidosis.

Arginine Relieves the Inflammatory Response and Enhances the Casein Expression in Bovine Mammary Epithelial Cells Induced by Lipopolysaccharide.

As one of functional active amino acids, L-arginine holds a key position in immunity. However, the mechanism that arginine modulates cow mammary inflammatory response in ruminant is unclear. Therefore, this study was conducted to investigate the effects of L-arginine on inflammatory response and casein expression after challenging the bovine mammary epithelial cells (BMECs) with lipopolysaccharide (LPS). The cells were divided into four groups, stimulated with or without LPS (10 µg/mL) and treated with or without arginine (100 µg/mL) for 12 h. The concentration of proinflammatory cytokines, inducible nitric oxide synthase (iNOS), mammalian target of rapamycin (mTOR), and Toll-like receptor 4 (TLR4) signaling pathways as well as the casein was determined. The results showed that arginine reduced the LPS-induced production like IL-1ß, IL-6, TNF-α, and iNOS. Though the expression of NF-κB was attenuated and the mTOR signaling pathway was upregulated, arginine had no effect on TLR4 expression. In addition, our results show that the content of ß-casein and the total casein were enhanced after arginine was supplemented in LPS-induced BMECs. In conclusion, arginine could relieve the inflammatory reaction induced by LPS and enhance the concentration of ß-casein and the total casein in bovine mammary epithelial cells.

Lower ω-6/ω-3 Polyunsaturated Fatty Acid Ratios Decrease Fat Deposition by Inhibiting Fat Synthesis in Gosling.

The objective of the current study was to investigate the effects of dietary ω-6/ω-3 polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ω-6/ω-3 PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ω-6/ω-3 PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ω-6/ω-3 PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings.

Effects of supplementation of rumen-protected choline on growth performance, meat quality and gene expression in longissimus dorsi muscle of lambs.

This study determined the effects of rumen-protected choline (RPC) on growth performance, blood lipids, meat quality and expression of genes involved in fatty-acid metabolism in young lambs. A total of 24 Dorper × Hu lambs (about 20 kg body weight) were kept in individual pens and fed diets with 0%, 0.25%, 0.50% and 0.75% RPC for 60 d. Supplementation of 0.25% RPC increased average daily gain of lambs, whereas treatments had no significant effect on feed intake. The pH values of meat were increased at 0.25% RPC and both, dripping loss and shear force of meat, were significantly decreased in RPC-supplemented lambs. No significant changes were observed for dressing percentage and intramuscular fat. RPC supplementations had no significant effect on the concentrations of triglycerides and cholesterols in serum, but the concentration of high-density lipoprotein was decreased at 0.50% RPC and that of low-density lipoprotein was increased at 0.75% RPC. In m. longissimus dorsi, the expressions of cluster of differentiation 36 (CD36), acetyl-CoA carboxylase (ACC) and fatty-acid synthase (FASN) genes were increased at 0.25% RPC. Supplementation of 0.75% RPC increased the expressions of lipoprotein lipase (LPL) and FASN genes, decreased the expression of ACC gene and had no effect on CD36 gene. The results of this study showed that supplementation of 0.25% RPC could promote growth performance of lambs and improve meat quality. This may be mediated by effects on blood lipid profiles and the metabolism of fatty acids in skeleton muscles. However, the beneficial effects of 0.25% RPC supplementation need to be validated with a larger number of animals. Higher doses, particularly 0.75% RPC, showed adverse effects on live weight gain and ACC expression.

Effect of Moringa oleifera leaf polysaccharide on the composition of intestinal microbiota in mice with dextran sulfate sodium-induced ulcerative colitis.

Moringa oleifera (M. oleifera) is a natural plant that has excellent nutritional and medicinal potential. M. oleifera leaves (MOL) contain several bioactive compounds. The aim of this study was to evaluate the potential effect of MOL polysaccharide (MOLP) on intestinal flora in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. DSS-induced colitis was deemed to be a well-characterized experimental colitis model for investigating the protective effect of drugs on UC. In this study, we stimulated the experimental mice with DSS 4% for 7 days and prepared the high dose of MOLP (MOLP-H) in order to evaluate its effect on intestinal flora in DSS-induced UC mice, comparing three experimental groups, including the control, DSS model, and DSS + MOLP-H (100 mg/kg/day). At the end of the experiment, feces were collected, and the changes in intestinal flora in DSS-induced mice were analyzed based on 16S rDNA high throughput sequencing technology. The results showed that the Shannon, Simpson, and observed species indices of abundance decreased in the DSS group compared with the control group. However, the indices mentioned above were increased in the MOLP-H group. According to beta diversity analysis, the DSS group showed low bacterial diversity and the distance between the control and MOLP-H groups, respectively. In addition, compared with the control group, the relative abundance of Firmicutes in the DSS group decreased and the abundance of Helicobacter increased, while MOLP-H treatment improves intestinal health by enhancing the number of beneficial organisms, including Firmicutes, while reducing the number of pathogenic organisms, such as Helicobacter. In conclusion, these findings suggest that MOLP-H may be a viable prebiotic with health-promoting properties.

A retrospective study on the effect of statins on mortality and antimicrobial resistance among patients with Staphylococcus aureus bloodstream infection.

Introduction: There is insufficient evidence in statin on the treatment of Staphylococcus aureus (SA) infection, we observe and analyze the clinical outcomes and antibiotic resistance of SA bloodstream infections in patients who received statins. Methods: A retrospective study was carried out in SA bloodstream infection of hospitalized patients from January 2018 to August 2023. The 30-day attributable mortality, 30-day all-cause mortality and clinical data of patients who received statins and non-statins were compared. Results: A total of 74 patients with SA bloodstream infection were included, 32 (43.2%) patients received treatment with statins and 42 (56.8%) with non-statins. The incidence of methicillin-resistant SA (MRSA) was significantly lower in the statins group (15.6% vs. 38.1%, p = 0.034), however, no significant differences were observed in the mortality rate (p = 0.410). Conclusions: This study revealed the superiority of statins in reducing incidence of MRSA among SA bloodstream infection patients, but statins do not improve the 30-day mortality rate.

Gut microbiota contributes to bisphenol A-induced maternal intestinal and placental apoptosis, oxidative stress, and fetal growth restriction in pregnant ewe model by regulating gut-placental axis.

BACKGROUND: Bisphenol A (BPA) is an environmental contaminant with endocrine-disrupting properties that induce fetal growth restriction (FGR). Previous studies on pregnant ewes revealed that BPA exposure causes placental apoptosis and oxidative stress (OS) and decreases placental efficiency, consequently leading to FGR. Nonetheless, the response of gut microbiota to BPA exposure and its role in aggravating BPA-mediated apoptosis, autophagy, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and OS of the maternal placenta and intestine are unclear in an ovine model of gestation. RESULTS: Two pregnant ewe groups (n = 8/group) were given either a subcutaneous (sc) injection of corn oil (CON group) or BPA (5 mg/kg/day) dissolved in corn oil (BPA group) once daily, from day 40 to day 110 of gestation. The maternal colonic digesta and the ileum and placental tissue samples were collected to measure the biomarkers of autophagy, apoptosis, mitochondrial dysfunction, ERS, and OS. To investigate the link between gut microbiota and the BPA-induced FGR in pregnant ewes, gut microbiota transplantation (GMT) was conducted in two pregnant mice groups (n = 10/group) from day 0 to day 18 of gestation after removing their intestinal microbiota by antibiotics. The results indicated that BPA aggravates apoptosis, ERS and autophagy, mitochondrial function injury of the placenta and ileum, and gut microbiota dysbiosis in pregnant ewes. GMT indicated that BPA-induced ERS, autophagy, and apoptosis in the ileum and placenta are attributed to gut microbiota dysbiosis resulting from BPA exposure. CONCLUSIONS: Our findings indicate the underlying role of gut microbiota dysbiosis and gut-placental axis behind the BPA-mediated maternal intestinal and placental apoptosis, OS, and FGR. The findings further provide novel insights into modulating the balance of gut microbiota through medication or probiotics, functioning via the gut-placental axis, to alleviate gut-derived placental impairment or FGR. Video Abstract.

Integrative Meta-Analysis: Unveiling Genetic Factors in Meat Sheep Growth and Muscular Development through QTL and Transcriptome Studies.

OBJECTIVE: The study aimed to investigate the effects of castration on performance, carcass characteristics, and meat quality in sheep, as well as explore the expression of key genes related to metabolic pathways and muscle growth following castration. METHODS: A meta-analysis approach was utilized to analyze data from multiple studies to compare the performance, carcass characteristics, and meat quality of castrated sheep (wethers) with intact rams. Additionally, protein-protein interaction (PPI) networks, differential gene expression (DEG) interactions, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were examined to identify molecular mechanisms associated with fat metabolism and muscle development in sheep tails. RESULTS: The analysis revealed that castrated sheep (wethers) exhibited improved average daily gain, increased tenderness, lower backfat thickness, and a tendency for greater loin muscle area compared to intact rams. This suggests that castration promotes faster growth and results in leaner carcasses with potentially higher muscle content. Furthermore, the identification of downregulated DEGs like ACLY, SLC27A2, and COL1A1 and upregulated DEGs such as HOXA9, PGM2L1, and ABAT provides insights into the molecular mechanisms underlying fat deposition and muscle development in sheep. CONCLUSIONS: The findings support the practice of castration in sheep production as it enhances growth performance, leads to leaner carcasses with higher muscle content, and improves meat tenderness. The identified changes in gene expression offer valuable insights for further research into understanding the impact of castration on muscle development and fat metabolism in sheep. This meta-analysis contributes to the knowledge of molecular mechanisms involved in fat deposition in sheep, opening avenues for future investigations in livestock fat metabolism research.