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Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.

The objective of this study was to compare the properties of small intestinal fluid (SIF) from white- and yellow-feathered broilers fed variable dietary CP to test the hypothesis that digestive enzymes sourced from the SIF of yellow-feathered broilers could serve as a viable alternative for preparing in vitro SIF specifically for white-feathered broilers. Ten Arbor Acres Plus broilers (32 days of age) and 20 Chinese yellow chickens (51 days of age) were fitted with jejunal cannulas and assigned to dietary treatments as follows: 1) white-feathered broilers (BW of 4.08 ± 0.39 kg) fed diet 1 with CP of 19.88 %, 2) yellow-feathered broilers (BW of 2.89 ± 0.27 kg) fed diet 1, and 3) yellow-feathered broilers (BW of 2.84 ± 0.20 kg) fed diet 2 with CP of 16.32 %. Each treatment contained 10 replicates with 1 broiler in each replicate. Digestive enzyme activities, ion concentrations, pH, 16 amino acid (AA, excluding Tyr and Trp) contents, molecular weight distribution (MWD) of protein, hydrolysis rates on wheat starch, corn starch, casein, and soybean protein concentrate, and in vitro digestible energy of corn, soybean meal, and corn gluten meal were evaluated for SIF. Activities of chymotrypsin and amylase, pH, concentrations (mg/mL) of total amino acid (TAA) and 13 AA (excluding Pro, Cys, and Glu), and hydrolysis rates in casein or soybean protein concentrate were greater (P < 0.05), whereas MWD of protein from 19 to 23 kDa was lower (P < 0.05) in the SIF of yellow compared to white-feathered broilers fed diet 1. Furthermore, activities of chymotrypsin and amylase, concentrations of Na+, and Cl−, MWD of protein from 15 to 18 kDa were greater, while concentrations of K+ were lower in the SIF of yellow-feathered broilers fed diet 2 compared to white feathered broilers fed diet 1. Activities of chymotrypsin and amylase, K+ concentration, pH, TAA and 13 AA (excluding Pro, Cys, and Glu), hydrolysis rates in casein or soybean protein concentrate increased (P < 0.05), while concentrations of Na+ and Cl− (P < 0.05) decreased with dietary CP in SIF from yellow-feathered broilers. This experiment demonstrated diet composition and breed modulate digestive enzyme activities, ions (Na+, K+, Cl−), pH, and AA concentrations in the SIF. Our findings revealed no substantial difference in the hydrolytic characteristics of SIF from white-feathered broilers fed diet 1 and yellow-feathered broilers fed diet 2. Consequently, it is feasible to use digestive enzymes extracted from the SIF of yellow-feathered broilers to prepare simulated SIF for in vitro digestion of white-feathered broilers.

ABSTRACT: Enterococcus faecium (E. faecium) is an alternative to antibiotics, while the probiotic effect of short-term application in mature broiler chickens remains unclear. In the current study, 48 Arbor Acres male broilers were chosen to investigate the effects of E. faecium on growth performance, the gut microbiome and intestinal health during the finishing period. Forty-eight birds were randomly allocated to 4 treatment groups that were fed a corn-soybean meal basal diet (Con), a basal diet supplemented with 1 g/kg amoxicillin (ABX), 5×106 CFU/g encapsulated E. faecium (cEF), or 5×106 CFU/g uncoated E. faecium (EF) from d 33 to 42. The results showed that 10 d of antibiotic treatment decreased the growth performance of the broilers (P < 0.05). The feed conversion ratio of the cEF and EF groups were lower than that of the Con group by 0.13 and 0.07, respectively (P > 0.05). The abundance of viable ileal and cecal E. faecium in the cEF group was greater than that in the EF group (P < 0.05), and both groups were markedly greater than those in the Con and ABX groups (P < 0.05). The ABX treatment decreased the Shannon and Chao1 indices of the cecal microbiota, while the dietary E. faecium treatment resulted in significant differences in the β diversity of the ileal and cecal microbiota (P < 0.05). Mantel correlation revealed that the ileal microbiota at the genus level was significantly correlated with the growth performance of broilers, with Lactobacillus, Bacillus and Escherichia-Shigella showing positive and strong correlations (P < 0.05). In the ileum, the crypt depth was lower in the cEF group than in the Con group, but the villi height-to-crypt depth ratio was greater in the cEF group than in the other groups (P = 0.037). However, the expression of the ZO-2 and Occludin genes was downregulated in the E. faecium-fed birds (P < 0.05). In the cecum, the acetate, butyrate and total SCFA levels were greater in the EF group (P < 0.05), while the propionate, isobutyrate and isovalerate levels were lower in the ABX group (P < 0.05). In summary, 10 d of dietary supplementation with E. faecium markedly increased colonization in mature broilers and potentially improved growth performance by modulating the ileal microbiota. Encapsulation techniques could enable a slow release of E. faecium in the intestine, thereby reducing the negative impacts of rapid expansion of E. faecium on the intestinal epithelium.

ABSTRACT: The purpose of this study was to investigate the effects of coating technology on the cysteamine (CSH) release in the digestive tract and the growth-promoting effect of enteric-coating CSH in broilers. First, using the self-developed computer-controlled simulated digestion system to mimic the digestion process in vitro, the release of 2 coated CSH (CSH-I and CSH-Ⅱ) were studied. The results showed that less than 10% of CSH-I was released after gastric digestion and 52.35% of CSH-I was released with additional 4 h of small intestinal digestion. In contrast, 83.62% of CSH-Ⅱ was released during the gastric digestion. In order to verify the growth-promoting effects of CSH-I, a feeding trial was conducted in a completely randomized block arrangement with 3 treatments in 6 blocks, 5 chickens per replicate. Broilers were fed with corn-soybean meal diet either supplemented with 0 (CON), 200 mg/kg uncoated CSH (CSH) or 200 mg/kg CSH-I from d 7 to 42, respectively. Body weight and FI was recorded at d 21 and 42. Excreta were collected from d 39 to d 42 to determine the total tract retention (TTR) of dietary nutrients. In comparisons with controls, birds fed with CSH-I had greater BW, ADG, and ADFI and increased TTR of DM, gross energy (GE), NDF and hemicellulose (P < 0.05). In addition, duodenal villi height and surface area were also greater in those CSH-I-fed birds. In contrast, the growth performance of birds fed with uncoated CSH did not significantly differ from controls. Although the TTR of DM and GE was higher in birds fed with CSH than controls, no differences in small intestine morphology were noted. Thus, the type I coating (CSH-I) could be good enteric-coating technology to increase CSH release in the duodenum, improve digestion and duodenal morphology, and therefore growth performance in broilers.