Litter size influences rumen microbiota and fermentation efficiency, thus determining host early growth in goats

IntroductionMultiple litters are accompanied by low birth weight, low survival rates, and growth rates in goats during early life. Regulating rumen microbiota structure can indirectly or directly affect host metabolism and animal growth. However, the relationship between high litter size and rumen microbiome, rumen fermentation, and growth performance in goat kids is unclear.MethodsIn the present study, thirty 6-month-old, female goats were investigated, of which 10 goats were randomly chosen from single, twin and triplet goats respectively, and their birth weight was recorded. From birth, all goats were subjected to the same feed and management practices. Individual weaning and youth body weight were measured, and the rumen fluid samples were collected to characterize the bacterial communities and to determine the ruminal volatile fatty acids (VFA), free amino acids (AA), and free fatty acids (FA) concentration of those young goats.Results and DiscussionCompared with the single and twin goats, triplet goats have lower weaning and youth body weight and average daily gain (ADG). Ruminal propionate, butyrate, and total VFA were decreased in triplet goats. Meanwhile, ruminal AA, such as branched chain amino acids (BCAA), essential amino acids (EAA), unsaturated fatty acids (UFA), and monounsaturated fatty acids (MUFA) were decreased, while saturated fatty acids (SFA) and odd and branched chain fatty acids (OBCFA) were increased in triplet goats. Our results also revealed that litter size significantly affected the rumen bacterial communities, and triplet goats had a lower the Firmicutes: Bacteroidota ratio, the abundance of Firmicutes phylum, Rikenellaceae family, and Rikenellaceae RC9 gut group, and had a higher proportion of Prevotellaceae family, and several genera of Prevotellaceae, such as Prevotella, and unclassified f Prevotellaceae. Furthermore, Spearman’s correlation network analysis showed that the changes in the rumen bacteria were associated with changes in rumen metabolites. In conclusion, this study revealed that high litter size could bring disturbances to the microbial communities and decrease the rumen fermentation efficiency and growth performance, which can be utilized to better understand variation in microbial ecology that will improve growth performance in triplet goats

The Genome of the Netherlands: Design, and project goals

Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project

The role of gut fungi in Clostridioides difficile infection

Clostridioides difficile, the etiological agent of C. difficile infection (CDI), elicits a spectrum of diarrheal symptoms with varying severity and the potential to result in severe complications such as colonic perforation, pseudomembranous colitis, and toxic megacolon. The perturbation of gut microbiome, often triggered by antibiotic usage, represents the primary factor augmenting the risk of CDI. This underscores the significance of interactions between C. difficile and the microbiome in determining pathogen adaptability. In recent years, researchers have increasingly recognized the pivotal role played by intestinal microbiota in host health and its therapeutic potential as a target for medical interventions. While extensive evidence has been established regarding the involvement of gut bacteria in CDI, our understanding of symbiotic interactions between hosts and fungi within intestinal microbiota remains limited. Herein, we aim to comprehensively elucidate both composition and key characteristics of gut fungal communities that significantly contribute to CDI, thereby enhancing our comprehension from pharmacological and biomarker perspectives while exploring their prospective therapeutic applications for CDI

Nrf2 and Keap1 Abnormalities in 104 Lung Adenocarcinoma Cases and Association with Clinicopathologic Features

Background and objective There are significantly interindividual variations of the expression level of nuclear factor erythroid-2-related factor 2 (Nrf2) and/or Kelch-like ECH-associated protein 1 (Keap1) in our previous studies. It has been proven that Nrf2 or Keap1 is related to resistance of chemotherapeutic drugs and/or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, the expression of Nrf2 and Keap1 in lung adenocarcinoma patients with different “driver gene” is not clear. The aim of this study is to investigate the protein expression level of Nrf2 and Keap1 in lung adenocarcinoma and to elucidate the correlation between Nrf2 or Keap1 expression and the status of EGFR gene mutation and to determine the effects of Nrf2 and Keap1 on the patients. Methods Immunohistochemical analysis of Nrf2 and Keap1 in tumor specimens was performed in a total of 104 lung adenocarcinoma patients with the status of EGFR gene mutations or EGFR wide-type. Results The Nrf2 positive rate was 71.2% and Keap1 high expression rate was 34.6% in 104 patients. The Nrf2 positive rate significantly correlated with gender, stage and status of EGFR gene mutation (P0.05). The high expression of Keap1 was not significantly correlated with gender, age, smoking, differentiation, subtype of lung adenocarcinoma and status of EGFR gene mutation (P>0.05). The progression -free survival (PFS) and overall survival (OS) of the patients treated by EGFR-TKIs were significantly correlated with the expression level of Nrf2, but not with Keap1. The PFS and OS of the patients with Nrf2 high expression were significantly shorter than the patients with low/negative expression (P<0.05). Furthermore, Nrf2 high expression was the independent predictive factor for EGFR-TKIs induced PFS and OS (P<0.05). Conclusion The Nrf2 positive rate significantly correlated with the status of EGFR gene mutation in lung adenocarcinoma. The Nrf2 high expression significantly correlated with PFS and OS of EGFR-TKIs. Therefore, Nrf2 may be a biomarker for predicting response of EGFR-TKIs and a potential target for overcoming resistance of EGFR-TKIs

Regulation of Nutritional Metabolism in Transition Dairy Cows: Energy Homeostasis and Health in Response to Post-Ruminal Choline and Methionine.

This study investigated the effects of rumen-protected methionine (RPM) and rumen-protected choline (RPC) on energy balance, postpartum lactation performance, antioxidant capacity and immune response in transition dairy cows. Forty-eight multiparous transition cows were matched and divided into four groups: control, 15 g/d RPC, 15 g/d RPM or 15 g/d RPC + 15 g/d RPM. Diet samples were collected daily before feeding, and blood samples were collected weekly from the jugular vein before morning feeding from 21 days prepartum to 21 days postpartum. Postpartum dry matter intake (DMI) was increased by both additives (P < 0.05), and energy balance values in supplemented cows were improved after parturition (P < 0.05). Both RPC and RPM decreased the plasma concentrations of non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), but increased the plasma levels of glucose, very-low-density lipoprotein (VLDL) and apolipoprotein B100 (ApoB 100, P < 0.05). The supplements improved milk production (P < 0.05), and increased (P < 0.05) or tended to increase (0.05 < P < 0.10) the contents of milk fat and protein. The post-ruminal choline and methionine elevated the blood antioxidant status, as indicated by total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) activity and the vitamin E concentration (P < 0.05), and reduced the plasma malondialdehyde (MDA) level (P < 0.05). Furthermore, RPM and RPC elevated the plasma interleukin 2 (IL-2) concentration and the CD4+/CD8+ T lymphocyte ratio in peripheral blood (P < 0.05). Alternatively, the levels of tumor necrosis factor-α (TNF-α) and IL-6 were decreased by RPM and RPC (P < 0.05). Overall, the regulatory responses of RPC and RPM were highly correlated with time and were more effective in the postpartum cows. The results demonstrated that dietary supplementation with RPC and RPM promoted energy balance by increasing postpartal DMI and regulating hepatic lipid metabolism, improved postpartum lactation performance and enhanced antioxidant capacity and immune function of transition dairy cows

Effect of incubation temperature and substrate moisture on embryonic development, hatchling phenotypes and post-hatching growth in the Reeves’ Turtle, Mauremys reevesii

Background Reeves’ Turtles (Mauremys reevesii) are economically important in aquaculture in China. Understanding the effects of incubation temperature and substrate moisture on embryos and hatchlings is of great significance for improving the artificial culture of M. reevesii. However, available studies have not yet determined the thermal and hydric optima for M. reevesii eggs, and the potential interaction between the two factors. Methods In this study, eggs of M. reevesii were incubated at five temperature levels (23, 26, 29, 32 and 35 °C, fluctuation range ± 0.5 °C). In each temperature level, there were three substrate moisture levels (1:0.5, 1:0.9 and 1:1.2, weight ratio of vermiculite to water). Thus, a total of 15 combinations of temperature and moisture were used to examine the effects of incubation temperature and substrate moisture on incubation duration, hatching success, hatchling phenotypes, post-hatching growth and hatchling survival. Results Substrate moisture did not significantly affect most development parameters (except incubation duration and carapace width of hatchlings). Eggs incubated at low moisture level (1:0.5) had a longer incubation duration and produced hatchlings with smaller carapace widths than those incubated at medium (1:0.9) or high (1:1.2) moisture levels. Incubation temperature had a significant effect on incubation duration, hatching success, hatchling phenotypes and hatchling survival. Incubation duration decreased as incubation temperature increased. Eggs incubated at 23, 26 and 29 °C showed higher hatching success than those incubated at 32 and 35 °C. Hatchlings incubated at 32 °C were smaller in body size and mass than those incubated at 23, 26 and 29 °C. At 12 months of age, incubation temperature had no long-lasting effect on body mass, but hatchlings incubated at 23 and 35 °C had lower survival rates than those incubated at 26, 29 and 32 °C. For the development of embryos and hatchlings, the interaction between incubation temperature and substrate moisture was not significant. Conclusions Our results indicate that incubation temperature has a significant influence on the development of embryos and hatchlings of M. reevesii, while substrate moisture only significantly affects the incubation duration and carapace width of hatchlings. The combination of an incubation temperature of 29 ± 0.5 °C and a substrate moisture level of 1:1.2 represented optimal incubation conditions in this experiment. Such incubation conditions are helpful in obtaining higher hatching success, shorter incubation duration and higher survival rates for this aquaculture species

Clinical outcomes of advanced NSCLC patients with different EGFR exon 19 deletion subtypes treated with first‐line tyrosine kinase inhibitors: A single‐center ambispective cohort study

Abstract Background Clinical significance of various subtypes of epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) mutation in non‐small cell lung cancer (NSCLC) remains unclear. Methods We analyzed EGFR ex19del subtypes in NSCLC patients receiving first‐line tyrosine kinase inhibitor (TKI) therapy at our center (January 2018–June 2022) and correlated them with median progression‐free survival (mPFS) and median overall survival (mOS). Results We identified 17 different EGFR ex19del variants in 101 patients. Between the classic (E746_A750del, 64.4%) and nonclassic groups (the rest variants), no significant difference was observed in mPFS (13.5 vs. 19.3 months, p = 0.18) or mOS (44.1 vs. 77.0 months, p = 0.06). mPFS showed no significant difference between ex19del subgroups classified based on the presence of insertion (ex19delins), starting position or length of deletion. However, patients with ex19delins starting at E746 showed longer mPFS than the others (29.7 vs. 12.5 months, p = 0.04), and patients with ex19del of 15 nucleotides had shorter mOS than the others (44.1 vs. 77.0 months, p = 0.03). In multivariate analysis, ex19delins independently predicted a better PFS (HR = 0.311, p = 0.03); however, 15 nucleotide deletion was no longer associated with OS (HR = 0.181, p = 0.11). Secondary T790M mutation incidence was significantly higher in the ex19del subgroup starting at E746 than the others (64.7% vs. 30.8%, p = 0.04). Conclusions Our study revealed potential differences in TKI efficacy, resistance mechanism, and prognosis of various EGFR ex19del subtypes in NSCLC, underscoring the need for precise selection of first‐line therapy

Dynamics of methanogenesis, ruminal fermentation and fiber digestibility in ruminants following elimination of protozoa: a meta-analysis

Abstract Background Ruminal microbes are vital to the conversion of lignocellulose-rich plant materials into nutrients for ruminants. Although protozoa play a key role in linking ruminal microbial networks, the contribution of protozoa to rumen fermentation remains controversial; therefore, this meta-analysis was conducted to quantitatively summarize the temporal dynamics of methanogenesis, ruminal volatile fatty acid (VFA) profiles and dietary fiber digestibility in ruminants following the elimination of protozoa (also termed defaunation). A total of 49 studies from 22 publications were evaluated. Results The results revealed that defaunation reduced methane production and shifted ruminal VFA profiles to consist of more propionate and less acetate and butyrate, but with a reduced total VFA concentration and decreased dietary fiber digestibility. However, these effects were diminished linearly, at different rates, with time during the first few weeks after defaunation, and eventually reached relative stability. The acetate to propionate ratio and methane production were increased at 7 and 11 wk after defaunation, respectively. Conclusions Elimination of protozoa initially shifted the rumen fermentation toward the production of more propionate and less methane, but eventually toward the production of less propionate and more methane over time

Effects of fumaric acid supplementation on methane production and rumen fermentation in goats fed diets varying in forage and concentrate particle size

Abstract Background In rumen fermentation, fumaric acid (FA) could competitively utilize hydrogen with methanogenesis to enhance propionate production and suppress methane emission, but both effects were diet-dependent. This study aimed to explore the effects of FA supplementation on methanogenesis and rumen fermentation in goats fed diets varying in forage and concentrate particle size. Methods Four rumen-cannulated goats were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments: low or high ratio of forage particle size: concentrate particle size (Fps:Cps), without or with FA supplementation (24 g/d). Fps:Cps was higher in the diet with chopped alfalfa hay plus ground corn than in that with ground alfalfa hay plus crushed corn. Results Both increasing dietary Fps:Cps and FA supplementation shifted ruminal volatile fatty acid (VFA) patterns toward more propionate and less acetate in goats. An interaction between dietary Fps:Cps and FA supplementation was observed for the ratio of acetate to propionate (A:P), which was more predominant when FA was supplemented in the low-Fps:Cps diet. Methane production was reduced by FA, and the reduction was larger in the low-Fps:Cps diet (31.72%) than in the high-Fps:Cps diet (17.91%). Fumaric acid decreased ruminal total VFA concentration and increased ruminal pH. No difference was found in ruminal DM degradation of concentrate or alfalfa hay by dietary Fps:Cps or FA. Goats presented a lower ruminal methanogen abundance with FA supplementation and a higher B. fibrisolvens abundance with high dietary Fps:Cps. Conclusions Adjusting dietary Fps:Cps is an alternative dietary model for studying diet-dependent effects without changing dietary chemical composition. Fumaric acid supplementation in the low-Fps:Cps diet showed greater responses in methane mitigation and propionate increase