Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications.

Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation of ferrous ions (Fe2+) and lipid peroxides. As the metabolic hub of the body, the liver is crucial for iron storage and lipid metabolism. The liver seems to be closely related to ferroptosis through iron and lipid metabolism. Liver disease greatly threatens host health, and exploring effective interventions is essential. Mounting studies have demonstrated that ferroptosis is one of the possible pathogenic mechanisms involved in liver disease. Targeting ferroptosis may provide a promising opportunity for treating liver disease. However, drugs targeting ferroptosis are extremely limited. Therefore, it is an urgent need to develop new and safe ferroptosis regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, have recently shown great therapeutic potential in liver disease via modulating ferroptosis-related genes or pathways. Here, we outline the molecular mechanism of ferroptosis and systematically summarize the regulatory function of NAC on ferroptosis in liver disease. Finally, we discuss the application prospects and potential problems concerning NAC as ferroptosis regulators for managing liver disease.

Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant.

BACKGROUND: Although rumen development is crucial, hindgut undertakes a significant role in young ruminants' physiological development. High-starch diet is usually used to accelerate rumen development for young ruminants, but always leading to the enteral starch overload and hindgut dysbiosis. However, the mechanism behind remains unclear. The combination of colonic transcriptome, colonic luminal metabolome, and metagenome together with histological analysis was conducted using a goat model, with the aim to identify the potential molecular mechanisms behind the disrupted hindgut homeostasis by overload starch in young ruminants. RESULT: Compared with low enteral starch diet (LES), high enteral starch diet (HES)-fed goats had significantly higher colonic pathology scores, and serum diamine oxidase activity, and meanwhile significantly decreased colonic mucosal Mucin-2 (MUC2) protein expression and fecal scores, evidencing the HES-triggered colonic systemic inflammation. The bacterial taxa Prevotella sp. P4-67, Prevotella sp. PINT, and Bacteroides sp. CAG:927, together with fungal taxa Fusarium vanettenii, Neocallimastix californiae, Fusarium sp. AF-8, Hypoxylon sp. EC38, and Fusarium pseudograminearum, and the involved microbial immune pathways including the "T cell receptor signaling pathway" were higher in the colon of HES goats. The integrated metagenome and host transcriptome analysis revealed that these taxa were associated with enhanced pathogenic ability, antigen processing and presentation, and stimulated T helper 2 cell (TH2)-mediated cytokine secretion functions in the colon of HES goats. Further luminal metabolomics analysis showed increased relative content of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), and decreased the relative content of hypoxanthine in colonic digesta of HES goats. These altered metabolites contributed to enhancing the expression of TH2-mediated inflammatory-related cytokine secretion including GATA Binding Protein 3 (GATA3), IL-5, and IL-13. Using the linear mixed effect model, the variation of MUC2 biosynthesis explained by the colonic bacteria, bacterial functions, fungi, fungal functions, and metabolites were 21.92, 20.76, 19.43, 12.08, and 44.22%, respectively. The variation of pathology scores explained by the colonic bacterial functions, fungal functions, and metabolites were 15.35, 17.61, and 57.06%. CONCLUSIONS: Our findings revealed that enteral starch overload can trigger interrupted hindgut host-microbiome homeostasis that led to impaired mucosal, destroyed colonic water absorption, and TH2-mediated inflammatory process. Except for the colonic metabolites mostly contribute to the impaired mucosa, the nonnegligible contribution from fungi deserves more future studies focused on the fungal functions in hindgut dysbiosis of young ruminants. Video Abstract.

Multi-omics revealed the long-term effect of ruminal keystone bacteria and the microbial metabolome on lactation performance in adult dairy goats.

BACKGROUND: The increased growth rate of young animals can lead to higher lactation performance in adult goats; however, the effects of the ruminal microbiome on the growth of young goats, and the contribution of the early-life rumen microbiome to lifelong growth and lactation performance in goats has not yet been well defined. Hence, this study assessed the rumen microbiome in young goats with different average daily gains (ADG) and evaluated its contribution to growth and lactation performance during the first lactation period. RESULTS: Based on monitoring of a cohort of 99 goats from youth to first lactation, the 15 highest ADG (HADG) goats and 15 lowest ADG (LADG) goats were subjected to rumen fluid microbiome and metabolome profiling. The comparison of the rumen metagenome of HADG and LADG goats revealed that ruminal carbohydrate metabolism and amino acid metabolism function were enhanced in HADG goats, suggesting that the rumen fluid microbiome of HADG goats has higher feed fermentation ability. Co-occurrence network and correlation analysis revealed that Streptococcus, Candidatus Saccharimonans, and Succinivibrionaceae UCG-001 were significantly positively correlated with young goats' growth rates and some HADG-enriched carbohydrate and protein metabolites, such as propionate, butyrate, maltoriose, and amino acids, while several genera and species of Prevotella and Methanogens exhibited a negative relationship with young goats' growth rates and correlated with LADG-enriched metabolites, such as rumen acetate as well as methane. Additionally, some functional keystone bacterial taxa, such as Prevotella, in the rumen of young goats were significantly correlated with the same taxa in the rumen of adult lactation goats. Prevotella also enriched the rumen of LADG lactating goats and had a negative effect on rumen fermentation efficiency in lactating goats. Additional analysis using random forest machine learning showed that rumen fluid microbiota and their metabolites of young goats, such as Prevotellaceae UCG-003, acetate to propionate ratio could be potential microbial markers that can potentially classify high or low ADG goats with an accuracy of prediction of > 81.3%. Similarly, the abundance of Streptococcus in the rumen of young goats could be predictive of milk yield in adult goats with high accuracy (area under the curve 91.7%). CONCLUSIONS: This study identified the keystone bacterial taxa that influence carbohydrate and amino acid metabolic functions and shape the rumen fluid microbiota in the rumen of adult animals. Keystone bacteria and their effects on rumen fluid microbiota and metabolome composition during early life can lead to higher lactation performance in adult ruminants. These findings suggest that the rumen microbiome together with their metabolites in young ruminants have long-term effect on feed efficiency and animal performance. The fundamental knowledge may allow us to develop advanced methods to manipulate the rumen microbiome and improve production efficiency of ruminants. Video Abstract.

Active dry yeast supplementation benefits ruminal fermentation, bacterial community, blood immunoglobulins, and growth performance in young dairy goats, but not for intermittent supplementation.

This study evaluated the effects of active dry yeast (ADY) supplementation and supplementation strategies on ruminal fermentation, bacterial community, blood metabolites, and growth performance in young dairy goats. Sixty young female Guanzhong dairy goats of similar age (4.00 ± 0.50 months) and BW (19.65 ± 0.41 kg) were randomly divided into 3 groups (n = 20): (1) basal diet group (CON); (2) basal diet continuously supplemented with 3.0 g/goat per day commercial ADY (a proprietary strain of Saccharomyces cerevisiae with 5.0 × 109 cfu/g) group (CSY); (3) basal diet with intermittently supplemented ADY group (ISY; 5 d supplementation with ADY at 4.5 g/goat per day following 5 d of no supplementation). The experiment lasted 67 d with the first 7 d as an adaptive period. Rumen fluid and blood samples were collected bi-weekly. Data were analyzed using the MIXED procedure combined with the SLICE option in SAS. Specific orthogonal contrasts of ADY vs. CON and CSY vs. ISY were also analyzed. During the experimental period, ADY supplementation resulted in greater DMI (P = 0.03), ruminal acetate proportion (P < 0.01) and acetylesterase activity (P = 0.01), and blood contents of glucose (P = 0.01) and IgM (P = 0.02) and tended to have greater ADG (P = 0.05) and paunch girth (P = 0.06) than the CON, despite the propionate proportion (P = 0.03) and contents of total protein (P = 0.04) and IgA (P = 0.03) being lower. The lower ruminal NH3-N (P < 0.01) and blood urea nitrogen (P = 0.07) contents indicated greater nitrogen utilization with ADY supplementation. ADY supplementation showed persistent effects after it was stopped because the BW at 12 months of age (P = 0.03) and birth weight of lambs (P = 0.02) were greater than the CON. However, the ISY did not show those benefits and had significantly lower relative abundances of fiber-degrading related bacteria than the CSY. In conclusion, ADY supplementation, especially continuously supplemented, may enhance ADG and ADG:DMI ratio by improving DMI, ruminal cellulolytic bacteria abundance and enzyme activity, nitrogen utilization, and immune status. These findings provide a theoretical basis for the rational application of ADY and have important practical implications for the design of nutritional strategies in growing dairy goats.

Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.

The amino acid-stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase-mediated mTORC1 activation. Here, a highly conserved insulin-responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2-AKT1 is localized on lysosomes, and RagD-specific recruitment of mTORC2-AKT1 on lysosomes is identified as an essential step in insulin-AKT1-mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin-induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1-dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross-talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation.

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

Introduction: Multiple 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. Methods: In 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 Discussion: Compared 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.

Promotion of intestinal epithelial cell apoptosis by enterotoxigenic Escherichia coli via PKA-mediated inhibition of mTORC1 activation.

Enterotoxigenic Escherichia coli (ETEC) is the main causative pathogen of diarrhea. It causes acute watery diarrhea that leads to rapid dehydration and prostration within hours. ETEC is still an important cause of neonatal and post-weaning diarrhea in pigs. However, the mechanism underlying ETEC-induced diarrhea is not yet clear. In this study, we investigated these mechanisms and found that the mTORC1 pathway plays a role in the host response to ETEC F4 infection. Specifically, we found that ETEC F4 treatment significantly repressed mTORC1 activity as well as cell proliferation, promoted apoptosis and regulated the expression of diarrhea-related genes via the promotion of PKA-mediated phosphorylation of SIN1, which plays a critical role in the assembly of mTORC2. These findings indicate that PKA is a checkpoint for ETEC-induced diarrhea. In terms of potential therapeutic strategies, we found that ZnSO4 dramatically rescued ETEC F4-induced the inhibition of mTORC1 activity and cell viability and the induction of apoptosis and alterations in the expression of diarrhea-related genes. Thus, the present findings demonstrate that ETEC F4 influences mTORC1 activation by inhibiting the assembly of mTORC2 through PKA-mediated phosphorylation of SIN1. Further, supplementation with ZnSO4 is an effective strategy for blocking the effect of ETEC F4 on mTORC1 activation, and it may have potential clinical applications in the treatment of ETEC F4-induced diarrhea.

Farnesoid X Receptor (FXR) Regulates mTORC1 Signaling and Autophagy by Inhibiting SESN2 Expression.

SCOPE: The mechanistic target of rapamycin complex 1 (mTORC1), as a link between nutrients and autophagy, senses many nutrients in the microenvironment. A growing body of recent literature describes the function of bile acids (BAs) as versatile signaling molecules, while it remains largely unclear whether mTORC1 can sense BAs and the mechanism has not been studied. METHODS AND RESULTS: After treating LO2 cells with indicated concentration of chenodeoxycholic acid (CDCA) and farnesoid X receptor (FXR) inhibitor/activator for 6 h, it finds that CDCA and FXR significantly accelerate mTORC1 activation. The results of immunofluorescence indicate that CDCA and FXR inhibit cellular autophagy through activating mTORC1 pathway. In particular, these findings show that CDCA and FXR promote the lysosomal translocation and activation of mTORC1 in an amino acid-sensitive manner. Mechanistically, the transcriptomics data indicate that SESN2 is a checkpoint for mTORC1 lysosome translocation and activation induced by FXR, and knockdown SESN2 with siRNA suppresses the regulation of FXR on autophagy. CONCLUSION: These results indicate that FXR-induced decrease in SESN2 expression and activation of the mTORC1 pathway can control autophagy and be explored as potential therapeutic targets for enterohepatic and metabolic disorders.

Long-term and combined effects of N-[2-(nitrooxy)ethyl]-3-pyridinecarboxamide and fumaric acid on methane production, rumen fermentation, and lactation performance in dairy goats.

BACKGROUND: In recent years, nitrooxy compounds have been identified as promising inhibitors of methanogenesis in ruminants. However, when animals receive a nitrooxy compound, a high portion of the spared hydrogen is eructated as gas, which partly offsets the energy savings of CH4 mitigation. The objective of the present study was to evaluate the long-term and combined effects of supplementation with N-[2-(nitrooxy)ethyl]-3-pyridinecarboxamide (NPD), a methanogenesis inhibitor, and fumaric acid (FUM), a hydrogen sink, on enteric CH4 production, rumen fermentation, bacterial populations, apparent nutrient digestibility, and lactation performance of dairy goats. RESULTS: Twenty-four primiparous dairy goats were used in a randomized complete block design with a 2 × 2 factorial arrangement of treatments: supplementation without or with FUM (32 g/d) or NPD (0.5 g/d). All samples were collected every 3 weeks during a 12-week feeding experiment. Both FUM and NPD supplementation persistently inhibited CH4 yield (L/kg DMI, by 18.8% and 18.1%, respectively) without negative influence on DMI or apparent nutrient digestibility. When supplemented in combination, no additive CH4 suppression was observed. FUM showed greater responses in increasing the molar proportion of propionate when supplemented with NPD than supplemented alone (by 10.2% vs. 4.4%). The rumen microbiota structure in the animals receiving FUM was different from that of the other animals, particularly changed the structure of phylum Firmicutes. Daily milk production and serum total antioxidant capacity were improved by NPD, but the contents of milk fat and protein were decreased, probably due to the bioactivity of absorbed NPD on body metabolism. CONCLUSIONS: Supplementing NPD and FUM in combination is a promising way to persistently inhibit CH4 emissions with a higher rumen propionate proportion. However, the side effects of this nitrooxy compound on animals and its residues in animal products need further evaluation before it can be used as an animal feed additive.

A Metagenomic Insight Into the Hindgut Microbiota and Their Metabolites for Dairy Goats Fed Different Rumen Degradable Starch.

High starch diets have been proven to increase the risk of hindgut acidosis in high-yielding dairy animals. As an effective measurement of dietary carbohydrate for ruminants, studies on rumen degradable starch (RDS) and the effects on the gut microbiota diversity of carbohydrate-active enzymes (CAZymes), and Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology functional categories are helpful to understand the mechanisms between gut microbiota and carbohydrate metabolism in dairy goats. A total of 18 lactating goats (45.8 ± 1.54 kg) were randomly divided equally into three dietary treatments with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) on a DM basis for 5 weeks. Compared with the LRDS and MRDS groups, HRDS increased acetate molar proportion in the cecum. For the HRDS group, the abundance of family Ruminococcaceae and genus Ruminococcaceae UCG-010 were significantly increased in the cecum. For the LRDS group, the butyrate molar proportion and the abundance of butyrate producer family Bacteroidale_S24-7, family Lachnospiraceae, and genus Bacteroidale_S24-7_group were significantly increased in the cecum. Based on the BugBase phenotypic prediction, the microbial oxidative stress tolerant and decreased potentially pathogenic in the LRDS group were increased in the cecum compared with the HRDS group. A metagenomic study on cecal bacteria revealed that dietary RDS level could affect carbohydrate metabolism by increasing the glycoside hydrolase 95 (GH95) family and cellulase enzyme (EC 3.2.1.4) in the HRDS group; increasing the GH13_20 family and isoamylase enzyme (EC 3.2.1.68) in the LRDS group. PROBIO probiotics database showed the relative gene abundance of cecal probiotics significantly decreased in the HRDS group. Furthermore, goats fed the HRDS diet had a lower protein expression of Muc2, and greater expression RNA of interleukin-1ß and secretory immunoglobulin A in cecal mucosa than did goats fed the LRDS diet. Combined with the information from previous results from rumen, dietary RDS level altered the degradation position of carbohydrates in the gastrointestinal (GI) tract and increased the relative abundance of gene encoded enzymes degrading cellulose in the HRDS group in the cecum of dairy goats. This study revealed that the HRDS diet could bring disturbances to the microbial communities network containing taxa of the Lachnospiraceae and Ruminococcaceae and damage the mucus layer and inflammation in the cecum of dairy goats.

Physically effective neutral detergent fiber improves chewing activity, rumen fermentation, plasma metabolites, and milk production in lactating dairy cows fed a high-concentrate diet.

Subacute ruminal acidosis (SARA) continues to be a common and costly metabolic disorder in high-producing dairy cows worldwide. The objective of this study was to evaluate if increasing the concentration of physically effective neutral detergent fiber (peNDF) in diets can reduce the risk of SARA in cows fed a high-concentrate diet. Thirty second-parity Holstein cows in mid lactation (131 ± 8.3 d in milk) were randomly allocated to 3 dietary treatments (10 dairy cows per group): high (11.3%, high peNDF8.0), medium (10.6%, medium peNDF8.0), or low (9.0%, low peNDF8.0) concentration of peNDF8.0. The diets were prepared by mixing the same total mixed ration (57% concentrate and 43% roughages) for 10, 18, or 60 min, respectively. The treatments were fed for 36 d with 21 d for adaptation and 15 d for sampling. The peNDF8.0 intake was positively correlated with the peNDF8.0 concentration. Chewing and ruminating times adjusted for dry matter intake and NDF intake were linearly increased with the increased dietary peNDF8.0 concentration. The high peNDF8.0 diet decreased the number of meals per day. The increased dietary peNDF8.0 concentration linearly increased the rumen fluid pH, the molar percentage of acetate and isobutyrate, acetate-to-propionate ratio, and ammonia nitrogen concentration, but linearly decreased the molar percentages of propionate and valerate. The total VFA concentration and the molar percentages of butyrate and isovalerate remained unchanged. Meanwhile, the increase in the peNDF8.0 concentration of the diet linearly increased the activities of carboxymethyl cellulase, avicelase, ß-glucanase, and ferulic acid esterase in rumen fluid, but did not affect the activities of xylanase. Total plasma antioxidant capacity, γ-glutamyl transpeptidase activity, and plasma concentrations of total protein, albumin, creatinine, and malondialdehyde were linearly decreased by the increased dietary peNDF8.0 concentration. The increase in peNDF8.0 concentration raised the plasma concentrations of glucose, triglyceride, cholesterol, and blood urea nitrogen. Somatic cell counts in the milk were positively correlated with the dietary peNDF8.0 concentration. The feed and milk energy efficiencies were unaffected by the treatments. Shortening the total mixed ration mixing time may be a practical strategy to increase the peNDF8.0 concentration and reduce the risk of SARA in dairy cows fed high-concentrate diets.

High Rumen-Degradable Starch Diet Promotes Hepatic Lipolysis and Disrupts Enterohepatic Circulation of Bile Acids in Dairy Goats.

BACKGROUND: High rumen-degradable starch (RDS) diets decrease milk fat. The increase of LPS in plasma associated with increased RDS impairs liver function, immune response and lipid metabolism, which depress the precursors for milk fat. OBJECTIVE: This study investigated the mechanism of depression of milk fat precursors in the liver and small intestine of dairy goats fed different RDS diets. METHOD: Eighteen Guanzhong lactating goats (second lactation, 45.8 ± 1.54 kg) and 6 ruminally cannulated dairy goats (aged 2-3 y, 54.0 ± 2.40 kg) were fed 3 different diets with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) for 36 and 21 d, respectively, in experiments 1 and 2. The liver metabolites and jejunal microbiota in experiment 1 and LPS concentrations in rumen fluid and plasma in experiment 2 were measured. One-way ANOVA was used to analyze the biochemical parameters and mRNA or protein expression. The MIXED procedure was used to analyze LPS concentrations. RESULTS: In experiment 1, the HRDS diet showed increased activity of alkaline phosphatase (27.4 to 41.4 U/L) in plasma (P < 0.05) compared with LRDS treatment. The HRDS diet significantly increased the hepatic concentrations of l-carnitine (129%), l-palmitoylcarnitine (306%), taurochenodeoxycholate (856%), and taurodeoxycholic acid (588%) in liver (variable importance in the projection > 1, P < 0.10) compared with the LRDS treatment. Goats fed the HRDS diet had 33.6% greater liver protein expression of carnitine palmitoyltransferase-1 (P < 0.05), and greater relative abundance of Firmicutes and Ruminococcus 2 in the jejunal content (linear discriminant analysis > 2.0, P < 0.05) than did goats fed LRDS diet. In experiment 2, goats fed the HRDS diet had greater LPS concentrations in rumen fluid (7.57 to 13.6 kEU/mL) and plasma (0.037 to 0.179 EU/mL) (P < 0.05) than did goats fed LRDS diet. CONCLUSIONS: Feeding the HRDS diet promoted hepatic lipid ß-oxidation and disrupted phospholipid and bile acids metabolisms in liver, thereby reducing the supply of lipogenic precursors to the mammary gland in dairy goats.

Specific enrichment of microbes and increased ruminal propionate production: the potential mechanism underlying the high energy efficiency of Holstein heifers fed steam-flaked corn.

Corn grain has a high starch content and is used as main energy source in ruminant diets. Compared with finely ground corn (FGC), steam-flaked corn (SFC) could improve the milk yield of lactating dairy cows and the growth performance of feedlot cattle, but the detailed mechanisms underlying those finding are unknown. The rumen microbiome breaks down feedstuffs into energy substrates for the host animals, and contributes to feed efficiency. Therefore, the current study was conducted to investigate the ruminal bacterial community changes of heifers fed differently processed corn (SFC or FGC) using 16S rRNA sequencing technologies, and to uncover the detailed mechanisms underlying the high performance of ruminants fed the SFC diet. The results revealed that different processing methods changed the rumen characteristics and impacted the composition of the rumen bacteria. The SFC diet resulted in an increased average daily gain in heifers, an increased rumen propionate concentration and a decreased rumen ammonia nitrogen concentration. The relative abundance of the phylum Firmicutes and Proteobacteria were tended to increase or significantly increased in the heifers fed SFC diet compared with FGC diet. In addition, the relative abundance of amylolytic bacteria of the genera Succinivibrio, Roseburia and Blautia were elevated, and the cellulolytic bacteria (Ruminococcaceae_UCG-014 and Ruminococcaceae_UCG-013) were decreased by the steam flaking method. Spearman correlation analysis between the ruminal bacteria and the microbial metabolites showed that the rumen propionate concentration was positively correlated with genera Succinivibrio and Blautia abundance, but negatively correlated with genera Ruminococcaceae_UCG-014 abundance. Evident patterns of efficient improvement in rumen propionate and changes in rumen microbes to further improve feed conversion were identified. This observation uncovers the potential mechanisms underlying the increased efficiency of the SFC processing method for enhancing ruminant performance.

Stable Subloop Behavior in Ferroelectric Si-Doped HfO2.

The recent demand for analogue devices for neuromorphic applications requires modulation of multiple nonvolatile states. Ferroelectricity with multiple polarization states enables neuromorphic applications with various architectures. However, deterministic control of ferroelectric polarization states with conventional ferroelectric materials has been met with accessibility issues. Here, we report unprecedented stable accessibility with robust stability of multiple polarization states in ferroelectric HfO2. Through the combination of conventional voltage measurements, hysteresis temperature dependence analysis, piezoelectric force microscopy, first-principles calculations, and Monte Carlo simulations, we suggest that the unprecedented stability of intermediate states in ferroelectric HfO2 is due to the small critical volume size for nucleation and the large activation energy for ferroelectric dipole flipping. This work demonstrates the potential of ferroelectric HfO2 for analogue device applications enabling neuromorphic computing.

Ferroelectric Polarization-Switching Dynamics and Wake-Up Effect in Si-Doped HfO2.

The ferroelectricity in ultrathin HfO2 offers a viable alternative to ferroelectric memory. A reliable switching behavior is required for commercial applications; however, many intriguing features of this material have not been resolved. Herein, we report an increase in the remnant polarization after electric field cycling, known as the "wake-up" effect, in terms of the change in the polarization-switching dynamics of a Si-doped HfO2 thin film. Compared with a pristine specimen, the Si-doped HfO2 thin film exhibited a partial increase in polarization after a finite number of ferroelectric switching behaviors. The polarization-switching behavior was analyzed using the nucleation-limited switching model characterized by a Lorentzian distribution of logarithmic domain-switching times. The polarization switching was simulated using the Monte Carlo method with respect to the effect of defects. Comparing the experimental results with the simulations revealed that the wake-up effect in the HfO2 thin film is accompanied by the suppression of disorder.

In Situ Infrared Absorption Study of Plasma-Enhanced Atomic Layer Deposition of Silicon Nitride.

Despite the success of plasma-enhanced atomic layer deposition (PEALD) in depositing quality silicon nitride films, a fundamental understanding of the growth mechanism has been difficult to obtain because of lack of in situ characterization to probe the surface reactions noninvasively and the complexity of reactions induced/enhanced by the plasma. These challenges have hindered the direct observation of intermediate species formed during the reactions. We address this challenge by examining the interaction of Ar plasma using atomically flat, monohydride-terminated Si(111) as a well-defined model surface and focusing on the initial PEALD with aminosilanes. In situ infrared and X-ray photoelectron spectroscopy reveals that an Ar plasma induces desorption of H atoms from H-Si(111) surfaces, leaving Si dangling bonds, and that the reaction of di-sec-butylaminosilane (DSBAS) with Ar plasma-treated surfaces requires the presence of both active sites (Si dangling bonds) and Si-H; there is no reaction on fully H-terminated or activated surfaces. By contrast, high-quality hydrofluoric acid-etched Si3N4 surfaces readily react with DSBAS, resulting in the formation of O-SiH3. However, the presence of back-bonded oxygen in O-SiH3 inhibits H desorption by Ar or N2 plasma, presumably because of stabilization of H against ion-induced desorption. Consequently, there is no reaction of adsorbed aminosilanes even after extensive Ar or N2 plasma treatments; a thermal process is necessary to partially remove H, thereby promoting the formation of active sites. These observations are consistent with a mechanism requiring the presence of both undercoordinated nitrogen and/or dangling bonds and unreacted surface hydrogen. Because active sites are involved, the PEALD process is found to be sensitive to the duration of the plasma exposure treatment and the purge time, during which passivation of these sites can occur.

Effect of Bacillus amyloliquefaciens-based Direct-fed Microbial on Performance, Nutrient Utilization, Intestinal Morphology and Cecal Microflora in Broiler Chickens.

The present study was conducted to evaluate the effect of the dietary supplementation of Bacillus amyloliquefaciens-based direct-fed microbial (DFM) on growth performance, nutrient utilization, intestinal morphology and cecal microflora in broiler chickens. A total of two hundred and eighty eight 1-d-old Arbor Acres male broilers were randomly allocated to one of four experimental treatments in a completely randomized design. Each treatment was fed to eight replicate cages, with nine birds per cage. Dietary treatments were composed of an antibiotic-free basal diet (control), and the basal diet supplemented with either 15 mg/kg of virginiamycin as antibiotic growth promoter (AGP), 30 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 30) or 60 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 60). Experimental diets were fed in two phases: starter (d 1 to 21) and finisher (d 22 to 42). Growth performance, nutrient utilization, morphological parameters of the small intestine and cecal microbial populations were measured at the end of the starter (d 21) and finisher (d 42) phases. During the starter phase, DFM and virginiamycin supplementation improved the feed conversion ratio (FCR; p<0.01) compared with the control group. For the finisher phase and the overall experiment (d 1 to 42) broilers fed diets with the DFM had better body weight gain (BWG) and FCR than that of control (p<0.05). Supplementation of virginiamycin and DFM significantly increased the total tract apparent digestibility of crude protein (CP), dry matter (DM) and gross energy during both starter and finisher phases (p<0.05) compared with the control group. On d 21, villus height, crypt depth and villus height to crypt depth ratio of duodenum, jejunum, and ileum were significantly increased for the birds fed with the DFM diets as compared with the control group (p<0.05). The DFM 30, DFM 60, and AGP groups decreased the Escherichia coli population in cecum at d 21 and d 42 compared with control group (p<0.01). In addition, the population of Lactobacillus was increased in DFM 30 and DFM 60 groups as compared with control and AGP groups (p<0.01). It can be concluded that Bacillus amyloliquefaciens-based DFM could be an alternative to the use of AGPs in broilers diets based on plant protein.

Density functional theory study on the full ALD process of silicon nitride thin film deposition via BDEAS or BTBAS and NH3.

A detailed reaction mechanism has been proposed for the full ALD cycle of Si3N4 deposition on the ß-Si3N4(0001) surface using bis(diethylamino)silane (BDEAS) or bis(tertiarybutylamino)silane (BTBAS) as a Si precursor with NH3 acting as the nitrogen source. Potential energy landscapes were derived for all elementary steps in the proposed reaction network using a periodic slab surface model in the density functional approximation. Although the dissociative reactivity of BTBAS was slightly better than that of BDEAS, the thermal deposition process was still found to be an inherently high temperature process due to the high activation energies during the dissociative chemisorption of both precursors and the surface re-amination steps. These results underline the need to develop new precursors and alternative nitrogen sources when low temperature thermal silicon nitride films are targeted.

Determination and prediction of the energy content and amino acid digestibility of peanut meals fed to growing pigs.

Two experiments were conducted to determine the content of digestible energy (DE) and metabolisable energy (ME) as well as the apparent ileal digestibility (AID) and standardised ileal digestibility (SID) of amino acids in peanut meal (PNM) for growing pigs. In Experiment 1, 78 growing pigs (46.8 ± 2.6 kg) were randomly allotted to 1 of 13 diets, including a corn-soya bean meal basal diet and 12 PNM test diets. In Experiment 2, 12 growing barrows (48.7 ± 2.8 kg) were allotted to one of two 6 × 6 Latin squares. The treatments include a N-free diet and 10 PNM test diets. The results of Experiment 1 showed that the DE and ME differed (p < 0.05) among the 12 PNM samples. On a dry matter basis, the DE and ME content ranged from 14.5 to 16.4 MJ/kg (mean 15.6 MJ/kg) and from 12.7 to 15.5 MJ/kg (mean 13.9 MJ/kg), respectively. The apparent total tract digestibility (ATTD) of gross energy (GE) was 82.2%. The DE of PNM could be precisely predicted by equations including NDF combined with GE or crude protein (CP) with an R(2) value of 0.91 and 0.92, respectively. For the AID and SID for lysine, the results of Experiment 2 indicated variations among PNM sources ranging from 59.6% to 76.7% and 64.8% to 80.9%, respectively. However, for CP, variations for AID and SID were lower and ranged from 70.2% to 81.9% and 75.7% to 85.6%, respectively. The results indicate that the concentration of lysine was the best single predictor to estimate the digestibility of amino acids. However, further work is needed to investigate the reason for the variation in the digestibility of lysine and avoid processing procedures that are detrimental to lysine digestibility.

New volatile strontium and barium imidazolate complexes for the deposition of group 2 metal oxides.

We report the synthesis, characterization, and experimental density function theory-derived properties of new volatile strontium and barium imidazolate complexes, which under atomic layer deposition conditions using ozone as a reagent can deposit crystalline strontium oxide at 375 °C.