Systemic and local responses of cytokines and tissue histology following intramammary lipopolysaccharide challenge in dairy cows.

During bovine mastitis, immune responses include the release of cytokines and the recruitment of leukocytes, resulting in profound structural and functional changes in the mammary gland. Our aims were to delineate systemic and local cytokine responses and to quantify histological changes in the mammary tissue of lactating cows after acute intramammary lipopolysaccharide (LPS) challenge. Ten multiparous dairy cows were paired to either treatment (TRT) or control (CON) groups. For TRT cows, one side of the udder was randomly assigned to receive treatment with LPS (50 µg in 10 mL of saline, TL) into both the front and rear quarters; the contralateral quarters received saline (10 mL). Udder-halves of CON cows were similarly assigned randomly to receive either saline (10 mL, CS) or no infusion (untreated). Temporal changes in the concentrations of 15 cytokines in the blood (0, 3, 6, 12, and 24 h relative to the LPS infusion) and in mammary tissue (0, 3, and 12 h) were determined, as were concomitant changes in mammary histology. The cytokines IL-6, IL-10, MCP-1, and MIP-1ß showed a systemic response as their concentrations were significantly different in the plasma of TRT cows as compared with CON cows after LPS challenge. The cytokines IL-1α, IL-1ß, IL-6, IL-8, IL-17A, IL-36RA, IP-10, MCP-1, MIP-1α, MIP-1ß, TNF-α, and VEGF-A showed a local response in TL glands, and 8 cytokines, IL-1ß, IL-6, IL-10, IL-17A, IL-36RA, IP-10, MIP-1ß, and VEGF-A showed systemic changes in the nonchallenged mammary glands adjacent to LPS-infused glands. Endotoxin challenge evoked changes in the histology of mammary tissue that included a 5.2- and 7.2-fold increases in the number of neutrophils in alveolar lumens at 3 h and 12 h, respectively. In summary, LPS challenge induced specific local and systemic responses in cytokine induction and elicited neutrophil infiltration in bovine mammary tissue.

Decomposition mechanism of 1,3,5-trinitro-2,4,6-trinitroaminobenzene under thermal and shock stimuli using ReaxFF molecular dynamics simulations.

To obtain atomic-level insights into the decomposition behavior of 1,3,5-trinitro-2,4,6-trinitroaminobenzene (TNTNB) under different stimulations, this study applied reactive molecular dynamics simulations to illustrate the effects of thermal and shock stimuli on the TNTNB crystal. The results show that the initial decomposition of the TNTNB crystal under both thermal and shock stimuli starts with the breakage of the N-NO2 bond. However, the C6 ring in TNTNB undergoes structural rearrangement to form a C3-C5 bicyclic structure at a constant high temperature. Then, the C3 and C5 rings break in turn. The main final products of TNTNB under shock are N2, CO2, and H2O, while NO,  N2, H2O and CO are formed instead at 1 atm under a constant high temperature. Pressure is the main reason for this difference. High pressure promotes the complete oxidation of the reactants.

Encapsulating aluminum nanoparticles into carbon nanotubes for combustion: a molecular dynamics study.

Metal nanoparticles are easily deactivated by migration-aggregation in combustion. Encapsulated nanoparticles are one of the tools for coping with the stability challenges of metal nanoparticles. The self-assembly details of aluminum nanoparticles (ANPs) encapsulated into carbon nanotubes (CNTs) were demonstrated by molecular dynamics simulations. The simulation results show that ANPs can completely self-roll into CNTs to form a stable core-shell structure by inertial force and van der Waals force. Inside the tubes, ANPs move toward the cap at a velocity of 2.27 Å ps-1. However, it increases to 3.17 Å ps-1 when near the cap of CNTs. The initiation of the ANPs' oxidation and degradation can be effectively checked by coating CNTs. The diffusion of the Al atoms in the encapsulated ANPs occurred earlier than their oxidation in combustion, verified by using ReaxFF molecular dynamics simulations. The morphological evolutions of the nanostructures in the initial combustion of the encapsulated ANPs are predicted. The interplay between the encapsulated ANPs' responses and external stimuli is classified into core-shell separation, shell damage, and core-shell burst, which provides insights into the oxidation mechanism of encapsulated nanoparticles.

Parenterally Delivered Methionyl-Methionine Dipeptide During Pregnancy Enhances Mammogenesis and Lactation Performance Over Free Methionine by Activating PI3K-AKT Signaling in Methionine-Deficient Mice.

BACKGROUND: Pregnancy-induced hypoaminoacidemia, l-methionine (Met) included, disturbs embryogenesis and may also affect breast function. Supplementation with the dipeptide l-methionyl-Met (Met-Met) may improve lactation performance. OBJECTIVE: We compared the effects of supplemental Met or Met-Met during pregnancy on mammogenesis and lactogenesis and investigated underlying mechanisms. METHODS: In experiment 1, 9-wk-old ICR mice (n = 72, ∼30 g) were divided into 3 groups. During the first 17 days of pregnancy (DP), the Control group was fed a diet with Met (8.2 g/kg) and saline was intraperitoneally injected, the Met group was fed a Met-devoid diet and 35% of the Met (92-mmo l Met) as contained in the Control diet was intraperitoneally injected, and the Met-Met group was fed the same diet and 70-mmo l Met plus 11-mmo l Met-Met was intraperitoneally injected. All animals were fed the Control diet after DP17 and during lactation. Mammogenesis, lactogenesis, transcriptome at DP17, and milk performance during lactation were examined. In experiment 2, 9-wk-old ICR mice (n = 55, ∼30 g) at DP0 were injected through the teat with adeno-associated virus for overexpression/inhibition of phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1), divided into the Control, Met, and Met-Met groups and received the same treatment as experiment 1 to examine mammogenesis and lactogenesis at DP17. RESULTS: In experiment 1, compared with the Met group, the Met-Met group showed higher (P < 0.05) mammary epithelium percentage (42%) and αS1-casein expression (84%) at DP17, milk yield (34%) and energy concentrations (8.7%) during lactation; transcriptomic analysis illustrated activated phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) signaling in the mammary glands of the Met-Met group (P-adj < 0.001). In experiment 2, overexpression of Pik3r1 enhanced (P < 0.05) the protective effect of Met-Met over Met on mammogenesis and ß-casein expression. CONCLUSION: Met-Met is more effective than Met in promoting mammogenesis and lactogenesis mainly by activation of PI3K-AKT signaling in Met-deficient mice.

Short communication: The essential role of N-glycosylation in the transport activity of bovine peptide transporter 2.

Bovine peptide transporter 2 (bPepT2), which mediates the absorption of di- and tripeptides in the bovine mammary gland, was predicted to contain multiple putative N-glycosylation sites of asparagine residues. N-Linked glycosylation is proven to be essential for the folding, stability, localization, and substrate binding of nutrient transporters and could therefore potentially have an essential role in the function of bPepT2. This study investigated the effect of mutagenesis of N-glycosylation sites on the transport function of bPepT2 in Chinese hamster ovary (CHO) cells. The bPepT2 cDNA was cloned and sequenced. BioXM (http://202.195.246.60/BioXM/) and TMHMM (http://www.cbs.dtu.dk/services/TMHMM-2.0/) software were used to predict the AA composition and transmembrane domain of bPepT2, respectively. The AA sequence of bPepT2 was predicted to have 12 transmembrane domains, with a large extracellular loop between the ninth and tenth transmembrane domains. All 5 putative N-glycosylation sites in this loop were altered by site-directed mutagenesis, and the mutant construct was transfected into CHO cells for transport activity assay. Compared with the wild type, the bPepT2 mutant had significantly lower uptake activity of ß-alanyl-l-lysyl-Nε-7-amino-4-methyl-coumarin-3-acetic acid (ß-Ala-Lys-AMCA), a model dipeptide. Treatment with tunicamycin, an inhibitor of N-linked glycosylation, reduced the uptake of ß-Ala-Lys-AMCA in CHO cells relative to the control group. Kinetic studies indicated that the Michaelis constant of bPepT2 was not affected by the mutation (98.03 ± 8.30 and 88.33 ± 4.23 µM for the wild type and the mutant, respectively), but the maximum transport activity was significantly reduced (40.29 ± 8.30 and 13.02 ± 2.95 pmol/min per milligram of protein for the wild type and the mutant, respectively). In summary, this study demonstrated that N-glycosylation is critical for the function of bPepT2.

Effects of methionine partially replaced by methionyl-methionine dipeptide on intestinal function in methionine-deficient pregnant mice.

This study was to compare the effects of parenteral supplementation of methionyl-methionine (Met-Met) or Met on intestinal barrier function in Met-deficient pregnant mice. Pregnant mice were randomly divided into three groups. The Control group was provided a diet containing Met and received i.p. injection of saline. The Met group was fed the same diet but without Met and received daily i.p. injection of 35% of the Met contained in the control diet. The Met-Met group was treated the same as the Met group, except that 25% of the Met injected was replaced with Met-Met. Met-Met promoted villus surface area in ileum compared with Met alone. In addition, the mRNA abundance of amino acid and glucose transporters in the small intestine was altered with Met-Met. Moreover, Met-Met increased tight junction protein and decreased apoptosis-related proteins expression in the jejunum and ileum. These results suggest that Met-Met can promote intestinal function over Met alone in Met-deficient mice.

Lysine Stimulates Protein Synthesis by Promoting the Expression of ATB0,+ and Activating the mTOR Pathway in Bovine Mammary Epithelial Cells.

Background: l-lysine (Lys) is a critical dietary nutrient for mammary gland development and milk production. However, the specific pathways of Lys utilization and how milk protein synthesis is affected in bovine mammary epithelial cells (BMECs) are poorly understood. Objective: We aimed to investigate the effects of Lys on milk protein synthesis and the mechanism of Lys uptake and catabolism in BMECs. Methods: BMECs were cultured in 0, 0.5, 1.0, 1.5, 2.0, 5.0, and 10.0 mmol Lys/L to detect cell viability, or cultured in 0-2.0 mmol Lys/L with l-[ring-3H5] phenylalanine to study the effect of Lys on protein turnover, or cultured in Krebs buffer with [U-14C] l-Lys to quantify Lys metabolism. In some experiments, BMECs were cultured in a conditioned medium alone or including 1.0 mmol Lys/L and 2-amino-endo-bicyclo [2.2.1] heptane-2-carboxylic acid (BCH) for 24 h to analyze the expression of amino acid transporter B (0+) (ATB0,+), mammalian target of rapamycin (mTOR), and Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) pathways. Results: Including 1.0 mmol Lys/L in cultures increased cell viability by 17-47% and protein synthesis by 7-23%, whereas protein degradation was inhibited by 4-64% compared with BMECs cultured with 0, 0.5, or 2.0 mmol Lys/L (all P ≤ 0.05). Studies that used [U-14C] l-Lys showed that most Lys was incorporated into proteins (90%), whereas the remainder was either oxidized into CO2 (4%) or used as a substrate for aspartate (3%) and histidine synthesis (3%). Furthermore, Lys significantly increased expression of ATB0,+ (71% mRNA and 44% protein), STAT5 (27% mRNA and 21% phosphorylated proteins), and mTOR (51% mRNA and 22% phosphorylated proteins) compared with cells without Lys. Conclusions: Lys promoted protein synthesis, mostly through enhancing uptake by ATB0,+ and the mTOR and JAK2-STAT5 pathways. Understanding the utilization of Lys in BMECs provides insights into the role of amino acid nutrition in bovine milk production.

Reactive molecular dynamics simulation of thermal decomposition for nano-aluminized explosives.

Aluminized explosives have important applications in civil construction and military armaments, but their thermal decomposition mechanisms are not well characterized. Here, the thermal decomposition of TNT, RDX, HMX and CL-20 on Al nanoparticles is examined by reactive dynamics simulations using a newly parameterized reactive force field with low gradient correction (ReaxFF-lg). Partially passivated Al nanoparticles were constructed and mixed with TNT, RDX, HMX and CL-20 crystals and then the mixed systems are heated to a high temperature in which the explosives are fully decomposed. The simulation results show that the aluminized explosives undergo three main steps of thermal decomposition, which were denoted "adsorption period" (0-20 ps), "diffusion period" (20-80 ps) and "formation period" (80-210 ps). These stages in sequence are the chemical adsorption between Al and surrounding explosive molecules (R-NO2-Al bonding), the decomposition of the explosives and the diffusion of O atoms into the Al nanoparticles, and the formation of final products. In the first stage, the Al nanoparticles decrease the decomposition reaction barriers of RDX (1.90 kJ g-1), HMX (1.95 kJ g-1) and CL-20 (1.18 kJ g-1), respectively, and decrease the decomposition reaction barrier of TNT from 2.99 to 0.29 kJ g-1. Comparing with the crystalline RDX, HMX and CL-20, the energy releases are increased by 4.73-4.96 kJ g-1 in the second stage. The number of produced H2O molecules increased by 25.27-27.81% and the number of CO2 molecules decreased by 47.73-68.01% in the third stage. These three stages are further confirmed by the evolutive diagram of the structure and temperature distribution for the CL-20/Al system. The onset temperatures (To) of generating H2O for all the aluminized explosives decrease, while those of generating CO2 for aluminized HMX and CL-20 increase, which are in accord with the experiment of aluminized RDX.

Molecular dynamic simulation for thermal decomposition of RDX with nano-AlH3 particles.

Molecular dynamic simulation of a high explosive, RDX, mixed with AlH3 nanoparticles was performed by a newly parameterized ReaxFF force field. Testing of the ReaxFF shows that the mean absolute errors of the densities and bond lengths between calculated and experimental values are less than 7% and 3%, respectively. Using the ReaxFF, effects of AlH3 nanoparticles with different radii on the thermal decomposition of RDX were revealed. A new mechanism of the generation and the consumption of H2 was discovered in the explosion. The H2 is released by AlH3 firstly and then it reacts with NO2 and CO2 from the decomposition of RDX, leading to an increase of H2O, NO and CO. Meanwhile, the size effect of AlH3 upon the reaction was also revealed. As a result, the number of produced H2O and CO2 molecules increases by 10.38% and 56.85%, respectively, when the radius of AlH3 nanoparticles decreases from 1.10 to 0.68 nm. This showed that RDX decomposes more completely with smaller AlH3 nanoparticles, which was further demonstrated by the analysis of reaction residues and diffusion coefficients.

Regulatory roles of Oct proteins in the mammary gland.

The expression of Oct-1 and -2 and their binding to the octamer motif in the mammary gland are developmentally and hormonally regulated, consistent with the expression of milk proteins. Both of these transcription factors constitutively bind to the proximal promoter of the milk protein gene ß-casein and might be involved in the inhibition or activation of promoter activity via interactions with other transcription factors or cofactors at different developmental stages. In particular, the lactogenic hormone prolactin and glucocorticoids induce Oct-1 and Oct-2 binding and interaction with both the signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid receptor on the ß-casein promoter to activate ß-casein expression. In addition, increasing evidence has shown the involvement of another Oct factor, Oct-3/4, in mammary tumorigenesis, making Oct-3/4 an emerging prognostic marker of breast cancer and a molecular target for the gene-directed therapeutic intervention, prevention and treatment of breast cancer. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin.

Methionyl-Methionine Promotes α-s1 Casein Synthesis in Bovine Mammary Gland Explants by Enhancing Intracellular Substrate Availability and Activating JAK2-STAT5 and mTOR-Mediated Signaling Pathways.

BACKGROUND: Interest is increasing in the role of peptide-bound amino acids (AAs) in milk protein synthesis because studies have found that the uptake of some essential AAs by the mammary gland cannot meet the requirements for milk protein synthesis. Although the role of dipeptides in milk protein synthesis is clearly established, little is known about the underlying mechanisms. OBJECTIVE: The objective of this study was to determine whether small peptides can be taken up intact by the peptide transporters in mammary tissue explants and the underlying mechanisms of the effects of methionyl-methionine (Met-Met) supplementation on milk protein synthesis. METHODS: Mammary tissue explants were cultured in conditional medium and then treated with different concentrations of Met-Met that replaced 0%, 5%, 10%, 15%, 20%, and 25% of free Met for another 24 h. In some experiments, explants were cultured with an optimal dose of Met-Met with or without the inhibitors of peptide transporter 2 [PepT2; diethylpyrocarbonate (DEPC), 0.1 mmol/L] and aminopeptidase N (APN; bestatin, 20 µmol/L) for 24 h. RESULTS: The substitutions of 15% free Met with Met-Met significantly promoted α-s1 casein (αs1-CN) expression in the mammary explants (P < 0.05). The inhibition of the PepT2 by DEPC or APN by bestatin significantly decreased the Met-Met-stimulated increase of αs1-CN expression (P < 0.05). Compared with the control group (0% Met-Met), absorption of Val, Met, Leu, Phe, Lys, and His was improved, and mRNA abundance of the neutral and basic AA transporter was increased in the 15% Met-Met group (P < 0.05). In addition, the mRNA abundance of the mammalian target of rapamycin (mTOR), p70 ribosomal S6 kinase 1 gene, eukaryotic initiation factor 4E binding protein 1 gene , Janus kinase 2 (JAK2), and signal transducer and activator of transcription 5 (STAT5) was increased in the 15% Met-Met-treated group (P < 0.05). CONCLUSION: Met-Met promoted αs1-CN synthesis in cultured bovine mammary gland explants, and this stimulation may be mediated by enhanced intracellular substrate availability and by activating JAK2-STAT5 and mTOR signaling pathways.

Biology of glucose transport in the mammary gland.

Glucose is the major precursor of lactose, which is synthesized in Golgi vesicles of mammary secretory alveolar epithelial cells during lactation. Glucose is taken up by mammary epithelial cells through a passive, facilitative process, which is driven by the downward glucose concentration gradient across the plasma membrane. This process is mediated by facilitative glucose transporters (GLUTs), of which there are 14 known isoforms. Mammary glands mainly express GLUT1 and GLUT8, and GLUT1 is the predominant isoform with a Km of ~10 mM and transport activity for mannose and galactose in addition to glucose. Mammary glucose transport activity increases dramatically from the virgin state to the lactation state, with a concomitant increase in GLUT expression. The increased GLUT expression during lactogenesis is not stimulated by the accepted lactogenic hormones. New evidence indicates that a possible low oxygen tension resulting from increased metabolic rate and oxygen consumption may play a major role in stimulating glucose uptake and GLUT1 expression in mammary epithelial cells during lactogenesis. In addition to its primary presence on the plasma membrane, GLUT1 is also expressed on the Golgi membrane of mammary epithelial cells and is likely involved in facilitating the uptake of glucose and galactose to the site of lactose synthesis. Because lactose synthesis dictates milk volume, regulation of GLUT expression and trafficking represents potentially fruitful areas for further research in dairy production. In addition, this research will have pathological implications for the treatment of breast cancer because glucose uptake and GLUT expression are up-regulated in breast cancer cells to accommodate the increased glucose need.

Current major advances in the regulation of milk protein gene expression.

During lactation, functionally differentiated mammary epithelial cells convert circulating nutrients into various milk components, providing all essential nutrients for the growth and development of mammal neonates. One of the major milk components is milk protein, which includes the casein and whey proteins. Regulation of milk protein gene expression is dependent on hormonal and developmental cues that modulate the activity of specific transcription factors and change the chromatin structure in mammary epithelial cells. Understanding the underlying mechanisms involved in mammary-specific milk protein gene regulation will help improve the yield, quality, and efficiency of milk production and identify important signaling factors and pathways involved in mammary development, differentiation, lactation, and disease. In this review we first review advances in the understanding of the regulatory mechanisms of milk protein genes by hormones, growth factors, and the extracellular matrix, with a focus on transcriptional regulation. We then discuss the relationship between chromatin structure and milk protein gene expression from an epigenetic perspective. Finally, we summarize recent achievements using the mammary gland as a bioreactor for producing pharmaceutical proteins for human use.

Differential regulation of GLUT1 and GLUT8 expression by hypoxia in mammary epithelial cells.

Glucose is a major substrate for milk synthesis and is taken up from the blood by mammary epithelial cells (MECs) through facilitative glucose transporters (GLUTs). The expression levels of GLUT1 and GLUT8 are upregulated dramatically in the mammary gland from late pregnancy through early lactation stages. This study aimed to test the hypothesis that this increase in GLUT1 and GLUT8 expression involves hypoxia signaling through hypoxia inducible factor-1α (HIF-1α) in MECs. Mouse mammary glands showed significantly more hypoxia in midpregnancy through early lactation stages compared with in the virgin stage, as stained by the hypoxia marker pimonidazole HCl. Treatment with hypoxia (2% O2) significantly stimulated glucose uptake and GLUT1 mRNA and protein expression, but decreased GLUT8 mRNA expression in bovine MECs. In MECs, hypoxia also increased the levels of HIF-1α protein in the nuclei, and siRNA against HIF-1α completely abolished the hypoxia-induced upregulation of GLUT1, while having no effect on GLUT8 expression. A 5'-RCGTG-3' core HIF-1α binding sequence was identified 3.7 kb upstream of the bovine GLUT1 gene, and HIF-1α binding to this site was increased during hypoxia. In conclusion, the mammary glands in pregnant and lactating animals are hypoxic, and MECs respond to this hypoxia by increasing GLUT1 expression and glucose uptake through a HIF-1α-dependent mechanism. GLUT8 expression, however, is negatively regulated by hypoxia through a HIF-1α-independent pathway. The regulation of glucose transporters through hypoxia-mediated gene transcription in the mammary gland may provide an important physiological mechanism for MECs to meet the metabolic demands of mammary development and lactation.

Collaborative interaction of Oct-2 with Oct-1 in transactivation of lactogenic hormones-induced ß-casein gene expression in mammary epithelial cells.

Octamer-binding transcription factor-1 (Oct-1) is found to mediate lactogenic hormones (prolactin and glucocorticoids, HP)-induced ß-casein gene expression in mammary alveolar secretory epithelial cells (MECs). The mammary gland also expresses Oct-2 isoform. In this study, we show that Oct-2 is also involved in HP-induced ß-casein expression. Oct-2 endogenously binds to the ß-casein promoter in MECs, and HP induce Oct-2 binding activity via mechanisms other than increasing Oct-2 expression or inducing Oct-2 translocation to the nucleus. Oct-2 transactivates HP-induced ß-casein gene expression and this function is exchangeable with Oct-1. In MECs, Oct-2 is found to physically interact with Oct-1 regardless of HP treatment. However, HP induce physical interactions of Oct-2 with both signal transducer and activator of transcription 5 (STAT5) and glucocorticoid receptor (GR). These results provided biochemical evidence that Oct-2 may form a heteromer with Oct-1 in induction of ß-casein gene expression by HP in MECs.

Methionyl-Methionine Dipeptide Enhances Mammogenesis and Lactogenesis by Suppressing the Expression of a Novel Long Noncoding RNA MGPNCR to Inhibit eIF4B Dephosphorylation.

Previous research has demonstrated that in pregnant mice deficient in l-methionine (Met), the mixture of the dipeptide l-methionyl-l-methionine (Met-Met) with Met was more effective than Met alone in promoting mammogenesis and lactogenesis. This study aimed to investigate the role of a novel long noncoding RNA (lncRNA), named mammary gland proliferation-associated lncRNA (MGPNCR), in these processes. Transcriptomic analysis of mammary tissues from Met-deficient mice, supplemented either with a Met-Met/Met mixture or with Met alone, revealed significantly higher MGPNCR expression in the Met group compared to the mixture group, a finding recapitulated in a mammary epithelial cell model. Our findings suggested that MGPNCR hindered mammogenesis and milk protein synthesis by binding to eukaryotic initiation factor 4B (eIF4B). This interaction promoted the dephosphorylation of eIF4B at serine-422 by enhancing its association with protein phosphatase 2A (PP2A). Our study sheds light on the regulatory mechanisms of lncRNA-mediated dipeptide effects on mammary cell proliferation and milk protein synthesis. These insights underscore the potential benefits of utilizing dipeptides to improve milk protein in animals and potentially in humans.

Heat stress affects mammary metabolism by influencing the plasma flow to the glands.

BACKGROUND: Environmental heat stress (HS) can have detrimental effects on milk production by compromising the mammary function. Mammary plasma flow (MPF) plays a crucial role in nutrient supply and uptake in the mammary gland. In this experiment, we investigated the physiological and metabolic changes in high-yielding cows exposed to different degrees of HS: no HS with thermal-humidity index (THI) below 68 (No-HS), mild HS (Mild-HS, 68 ≤ THI ≤ 79), and moderate HS (Mod-HS, 79 < THI ≤ 88) in their natural environment. Our study focused on the changes in blood oxygen supply and mammary glucose uptake and utilization. RESULTS: Compared with No-HS, the MPF of dairy cows was greater (P < 0.01) under Mild-HS, but was lower (P < 0.01) in cows under Mod-HS. Oxygen supply and consumption exhibited similar changes to the MPF under different HS, with no difference in ratio of oxygen consumption to supply (P = 0.46). The mammary arterio-vein differences in glucose concentration were lower (P < 0.05) under Mild- and Mod-HS than under no HS. Glucose supply and flow were significantly increased (P < 0.01) under Mild-HS but significantly decreased (P < 0.01) under Mod-HS compared to No-HS. Glucose uptake (P < 0.01) and clearance rates (P < 0.01) were significantly reduced under Mod-HS compared to those under No-HS and Mild-HS. Under Mild-HS, there was a significant decrease (P < 0.01) in the ratio of lactose yield to mammary glucose supply compared to that under No-HS and Mod-HS, with no difference (P = 0.53) in the ratio of lactose yield to uptaken glucose among different HS situations. CONCLUSIONS: Degrees of HS exert different influences on mammary metabolism, mainly by altering MPF in dairy cows. The output from this study may help us to develop strategies to mitigate the impact of different degrees of HS on milk production.

Fatty liver accompanies an increase in lactobacillus species in the hind gut of C57BL/6 mice fed a high-fat diet.

High-fat (HF) diets can produce obesity and have been linked to the development of nonalcoholic fatty liver disease and changes in the gut microbiome. To test the hypothesis that HF feeding increases certain predominant hind gut bacteria and development of steatohepatitis, C57BL/6 mice were fed an HF (45% energy) or low-fat (LF) (10% energy) diet for 10 wk. At the end of the feeding period, body weights in the HF group were 34% greater than those in the LF group (P < 0.05). These changes were associated with dramatic increases in lipid droplet number and size, inflammatory cell infiltration, and inducible nitric oxide (NO) synthase protein concentration in the livers of mice fed the HF diet. Consistent with the fatty liver phenotype, plasma leptin and tumor necrosis factor-α concentrations were also elevated in mice fed the HF diet, indicative of chronic inflammation. Eight of 12 pairs of polymerase chain reaction (PCR) primers for bacterial species that typically predominate hind gut microbial ecology generated specific PCR products from the fecal DNA samples. The amount of DNA from Lactobacillus gasseri and/or Lactobacillus taiwanensis in the HF group was 6900-fold greater than that in the LF group. Many of these bacteria are bile acid resistant and are capable of bile acid deconjugation. Because bile acids are regulators of hepatic lipid metabolism, the marked increase of gut L. gasseri and/or L. taiwanensis species bacteria with HF feeding may play a role in development of steatohepatitis in this model.

DFT studies on doping effect of Al12X: adsorption and dissociation of H2O on Al12X clusters.

The adsorption and reaction of H2O molecule on neutral X-centered icosahedronal Al12X clusters (X = Al, Mg, Zn, Ga, Ni, Fe, B, C, Si, P) were investigated by PW91, PBE, and PWC methods. Reaction energies and reaction barriers were determined. The spin states and the doped atoms have important influences on the Al12X geometries, density, electronic properties, and energy density of reaction between Al12X with a single H2O molecule. The energies of the neutral X-centered Al12X are lower than that of surface X-replaced Al12X with the exception of Al12Mg. The H2O dissociation on the Al12X (X = Mg, Zn, Ga, Ni, Fe) clusters have relatively low activation barriers, but large activation barriers for Al12X (X = B, C, Si, P). The activation barrier of water dissociation on the singlet Al12Fe cluster is the lowest, whereas the highest barrier is with the Al12C. The reaction of H2O with Al12Fe is the most exothermic. The center-Fe atom can move out to the surface after the adsorption and dissociation of H2O with an energy barrier of 172 kJ/mol. The results showed that the water dissociation on the Al12X cluster can be tuned by controllable X doping.

Adsorption of carbon dioxide on Al12X clusters studied by density functional theory: effect of charge and doping.

The adsorption of a CO2 molecule on neutral and charged X-centered icosahedron Al12X(±z) clusters (X = Al, Be, Zn, Ni, Cu, B, P; z = 0, 1) was investigated by the density functional PW91 and PWC methods. Optimized configurations corresponding to physisorption and chemisorption of CO2 were identified. The adsorption energies, activation barriers, and binding energies involving both the physisorption (Al12X(±z)·CO2-I) and chemisorption (Al12X(±z)·CO2-II) for CO2 were determined. The chemisorption of a CO2 molecule on the Al12X clusters (X is a metallic doping element) requires relatively low activation barriers. The lowest barrier was found to be with the Al12Be cluster. For the Al12X(-) clusters, the barriers are all higher than those of the neutral analogues. For the Al12X(+) clusters, two corresponding configurations are linked by a low-energy barrier, and CO2 molecule chemisorption on the Al12Be(+) cluster has the lowest barrier. The adsorption energies are larger than the energy barriers, which facilitates the chemisorption. The results show that carbon dioxide adsorbed on the Al12X(±z) clusters can be tuned by controllable X doping and the total number of valence electrons and suggest the potential application of Al12X(±z) nanostructures for carbon dioxide capture and activation.