Milk yield variation partially attributed to blood oxygen-mediated neutrophil activation in lactating dairy goats.

Blood oxygen is an essential component for numerous biological processes of mammalian animals. Milk production of ruminants largely relies on the supply of nutrients, such as glucose, amino acids and fatty acids. To define the regulatory role of blood oxygen availability in regard to milk production, seventy-five healthy Guanzhong dairy goats with similar body weight, days in milk and parities were selected. For each animal, milk yield was recorded and milk sample was collected to determine compositions. Milk vein blood was collected to determine parameters including blood gas, physio-biochemistry and haematology. Another blood sample was prepared for transcriptome and RT-qPCR. Results showed that both pressure of oxygen (pO2) in the milk vein (positively) and numbers of neutrophils in mammary vein (negatively) were associated with milk yield of the animals. To learn the role of pO2 in blood cell functionality, twelve animals (six with higher yield (H-group) and six with lower yield (L-group)) from seventy-five goats were selected. Compared with animals in L-group, goats in H-group were higher in pO2 but lower in pCO2, lactate, lactate dehydrogenase activity and neutrophil abundance in milk vein, compared with L-group. The blood transcriptome analysis suggested that compared with L-group, animals in H-group were depressed in functionality including neutrophil activation and metabolic pathways including glycolysis, NF-κB and HIF-1. Our result revealed that lower milk production could be associated with neutrophil activation responding to low pO2 in the mammary vein. In the meantime, we highlighted the potential importance of blood oxygen as a milk yield regulator.

Hypoxia-inducible factor-1α is involved in the response to heat stress in lactating dairy cows.

Hypoxia-inducible factor-1α (HIF-1α) is important in maintaining cellular oxygen homeostasis and cellular heat tolerance. To explore the role of HIF-1α in the response to heat stress (HS) in dairy cows, 16 Chinese Holstein cows (milk yield: 32 ± 4 kg/d, days in milk: 272 ± 7 d, parity: 2-3) were used to collect coccygeal vein blood and milk samples when cows were under mild (temperature-humidity index = 77) and moderate HS (temperature-humidity index = 84), respectively. Compared to cows under mild HS, the respiratory rate (P < 0.01), rectal temperature (P < 0.01), and blood concentrations of heat shock protein (HSP)70 (P < 0.01) and HSP27 (P < 0.01) were higher, but oxygen saturation (P = 0.02) and hemoglobin (P < 0.01) were lower in cows under moderate HS. Blood HIF-1α concentration was greater (P < 0.01) during moderate HS, indicating that HIF-1α is involved in lactating cows' response to HS. To confirm these findings, we collected coccygeal vein blood and milk samples from 59 dairy cows under moderate HS. The HIF-1α levels were correlated with the levels of heat shock transcription factor (HSF) (r = 0.7857, P < 0.01), HSP70 (r = 0.4543, P < 0.01) and HSP27 (r = 0.8782, P < 0.01). A comparison of 15 cows with higher HIF-1α (>482 ng/L) and 15 cows with lower HIF-1α levels (<439 ng/L) showed that reactive oxidative species were higher (P = 0.02), but superoxide dismutase (P < 0.01), total antioxidation capacity (P = 0.02) and glutathione peroxidase (P < 0.01) were lower in higher HIF-1α cows. These results suggested that HIF-1α may be indicative of the risk of oxidative stress in heat-stressed cows and may participate in the response of cows to HS by synergistically activating the expression of the HSP family with HSF.

Integrative network analysis revealed molecular mechanisms of urine urea output in lactating dairy cows: Potential solutions to reduce environmental nitrate contamination.

BACKGROUND: The enriched nitrogenous compounds in the dairy farms negatively affect the surrounding soil quality and air condition. The objective of this study is to investigate the transcriptomes of five key tissues involved in nitrogen metabolism and their changes under different diets to elucidate the molecular regulatory mechanisms of urine urea nitrogen (UUN) yield, one of the indicators of nitrogenous compound secretion of dairy cows. RESULTS: Cows fed high quality forage-based diet had lower UUN content and UUN yield, compared to those fed low quality forage (crop byproducts) based diets. From the transcriptomes of rumen, duodenum, jejunum, liver and udder, key driver genes and their UUN yield-associated functional gene networks were identified. In addition, the functional networks and expression of key drivers in various tissues (such as S100A8, CA1 and BPIFA2C in the duodenum; A2ML1, HMGCS2 and S100A12 in the jejunum; CYP2B6 and GLYCAM1 in the liver; APOE in the udder) changed in the cows fed crop byproducts based diet, which might be the predominant molecules to drive the increase UUN yield in these cows. CONCLUSION: The information suggested that gut, liver and udder play important roles in regulating UUN yield, which could regulate nitrogen excretion waste. These findings provide fundamental information on future nutritional intervention strategies to reduce the UUN yield from dairy cows fed human inedible crop byproducts, which is vital for a sustainable and environmentally friendly dairy industry.

Excessive supply of glucose elicits an NF-κB2-dependent glycolysis in lactating goat mammary glands.

During lactation, an improper glucose supply often threatens mammary gland (MG) health. However, information is limited on the metabolic trajectories and molecules that regulate lactating MGs with an excessive glucose supply. Based on the network analysis of transcriptome and microRNAs, we found that the oversupply of glucose-induced severe glucose metabolic disorders in MGs of lactating goats, shifting lactose synthesis to acute fermentative glycolysis which caused increased flux of glucose metabolism into lactate. Moreover, NF-κB2 played a key role in regulating glycolysis, exhibiting a metabolic shift when MGs had an excessive supply of glucose. In primary mammary epithelial cells, fermentative glycolysis, and intracellular concentration of reactive oxygen species (ROS) were reduced by ganoderic acid A through blocking NF-κB2, while activation of NF-κB2 with phorbol myristate acetate (PMA) upregulated fermentative glycolysis and increased cellular ROS accumulation under excessive glucose. Thus, we established an NF-κB2-targeting method to reform the metabolic shift toward glycolysis caused by glucose oversupply by integrating NF-κB2 blockade and intracellular ROS scavenging.

Prognostic potential of pre-partum blood biochemical and immune variables for postpartum mastitis risk in dairy cows.

BACKGROUND: Mastitis is the most frequent diseases for transition cows. Identification of potential biomarkers for diagnosis of mastitis is important for its prevention. Thus, this study was conducted to investigate blood variables related to lipid metabolism, oxidative stress and inflammation, and serum variables that are related to health in postpartum cows. RESULTS: Seventy-six healthy Holstein dairy cows at week 4 before calving were selected to collect blood samples from weeks - 4 to 4 weekly relative to calving, respectively. Milk yield and composition were recorded weekly. According to the cut-off of somatic cell counts (SCC) for diagnosis of mastitis, 33 cows with SCC ≥ 500,000 cells ml- 1, 20 cows with 200,000 cells ≤ SCC < 500,000 cells ml- 1, and 23 cows with SCC < 200,000 cells ml- 1 were defined as high, middle, and low SCC, respectively. Serum concentrations of ß-hydroxybutyrate were higher (P < 0.01) during all weeks, and non-esterified fatty acids were higher in high SCC than in low SCC cows from weeks - 3 to 2 relative to calving. Higher serum concentrations of superoxide dismutase (P < 0.01) and lower malondialdehyde levels (P < 0.01) in low SCC than in high SCC cows indicate that the latter suffered from oxidative stress. The difference analysis of the three groups suggested that none of the above-mentioned variables can be used as potential prognostic candidates. On the other hand, high SCC cows exhibited higher blood neutrophil to lymphocyte ratio (NLR, P < 0.01) and platelet to lymphocyte ratio (PLR, P < 0.01) than low SCC cows, with a higher NLR (P < 0.01) in middle SCC than in low SCC cows. The high SCC cows had lower levels of anti-inflammatory factors including IL-10 (P = 0.05), but higher levels of proinflammatory factors such as IL-6 (P < 0.01), TNF-α (P < 0.05), and PSGL-1 (P < 0.01) than low SCC cows. CONCLUSIONS: The significantly different NLR and PLR pre-partum between the middle and low SCC cows suggest their prognostic potential for postpartum mastitis risk.

Effects of body condition on the insulin resistance, lipid metabolism and oxidative stress of lactating dairy cows.

BACKGROUND: Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated. METHODS: The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment. RESULTS: The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups. CONCLUSIONS: Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.

Low-quality rice straw forage increases the permeability of mammary epithelial tight junctions in lactating dairy cows.

BACKGROUND: It is known that milking frequency and plasma hormones play important roles in regulating mammary permeability. However, it is still not known whether nutritional factors can influence udder permeability. DESIGN: This study was conducted to investigate mammary epithelial tight-junction permeability in lactating dairy cows fed different forage-based diets. Twenty mid-lactating dairy cows were allocated to ten blocks based on their parity and milk yield and then randomly assigned into rice straw-based diet and alfalfa-based diet groups. Both diets contained 15% corn silage and 55% concentrate (dry matter basis). In terms of forage sources, rice straw-based diets (RS) contained 30% rice straw, whereas alfalfa-based diets (AH) contained 23% alfalfa hay plus 7% Chinese wild rye hay. RESULTS: The concentrations of Na+ , Na+ /K+ ratio, bovine serum albumin, and plasmin in the milk, the plasma lactose concentration, and the mRNA abundance of BCL2 associated agonist of cell death, phosphatase and tensin homolog, and insulin like growth factor binding protein 5 in the mammary gland were greater in RS-fed cows than in AH-fed animals. Mammary expression of proliferating cell nuclear antigen and occludin was lower in RS-fed cows compared with the AH-fed group. The expressions of growth hormone receptor, claudin-1, -3, -4, and ZO-1 were similar in the two diet groups. CONCLUSION: The cows fed RS showed higher mammary alveolar permeability, likely due to its effect on proliferation/apoptosis rates of mammary epithelial cells. © 2018 Society of Chemical Industry.

Lactation performance and rumen fermentation in dairy cows fed a diet with alfalfa hay replaced by corn stover and supplemented with molasses.

OBJECTIVE: The objective of current study was to investigate the lactation performance and rumen fermentation characteristics of dairy cows fed a diet with alfalfa hay replaced by corn stover but supplemented with molasses. METHODS: Sixteen Holstein cows in mid-lactation were randomly assigned to 1 of 2 dietary treatments: i) alfalfa based diet (AH), and ii) corn stover based diet supplemented with molasses (CSM). The experiment was conducted according to a 2×2 crossover design with 22-d each period, consisting of 17 d for adaptation and 5 d for data and samples collection. RESULTS: Dry matter intake and milk yield were higher for cows fed AH than CSM (p<0.01). Milk protein content and nitrogen conversion were higher (p<0.05), while milk urea nitrogen was lower (p<0.01) for cows fed AH than CSM-fed cows. Contents of milk total solids, fat and lactose were not different between two groups (p>0.10). Total rumen volatile fatty acid concentration tended to be higher (p = 0.06) for cows fed AH than CSM-fed cows. Molar proportion of acetate was lower (p = 0.04), but valerate was higher (p = 0.02) in cows fed AH than CSM-fed cows. Rumen concentration of propionate, and isobutyrate, and ratio of acetate to propionate tended to be different (p<0.10) between two groups. The feed cost per kilogram of milk was lower in CSM than AH (p<0.01). No differences were found in feed efficiency and most plasma parameters tested (p>0.10). CONCLUSION: In comparison with AH diet, CSM diet could be fed to dairy cows without negative effect on feed efficiency, ruminal fermentation, but economically beneficial, indicating that CSM could be an alternative choice for dairy farms instead of AH to feed mid-lactation dairy cows.

Metabolomics Integrated with Transcriptomics Reveals a Subtle Liver Metabolic Risk in Dairy Cows Fed Different Crop By-products.

Ruminants make large contributions to sustainable agriculture by converting crop by-products into agricultural food. Multi-omics integrative analysis helps to uncover the underlying molecular mechanisms. The liver metabolome-transcriptome interface (LMTI) in dairy cows, including 3938 significant correlations (p < 0.01 and |ρ| > 0.6) among 772 genes, 306 metabolites, and 305 microRNAs, is first demonstrated. How different crop by-products, corn stover (CS) and rice straw (RS), affect the liver metabolic functions based on the LMTI is further analyzed. Compared to the CS-fed cows, 13 out of 24 metabolites have lower relative concentrations (variable importance projection > 1.0 and p < 0.05), and 51 out of 68 genes are downregulated in the RS group (p < 0.01 and fold change < -2). Integrated analysis of metabolomics and transcriptomics reveal that lipid metabolism is most enriched including 14 subpathways. The altered metabolites and genes revealed the enriched ketogenesis induced by the linoleic acid pathways (p = 0.017, topology value = 1), which is supported by blood and histomorphometric phenotypes. The above results indicate the foreseeable liver metabolic disorders when RS is fed to cows. These findings provide new insights into the liver metabolic mechanism and into crop by-products utilization using integrative omics technologies.

Regulation of fluid flow through the mammary gland of dairy cows and its effect on milk production: a systematic review.

Dairy milk consists of more than 85% water. Therefore, understanding the regulation of fluid absorption in the mammary gland is relevant to improving milk production. In recent decades, studies using different approaches, including blood flow, transmembrane fluid flow, tight junction, fluid flow of the paracellular pathway and functional mammary epithelial cell state, have been conducted aiming to investigate how mammary gland fluid absorption is regulated. However, the relationship between regulation mechanisms of fluid flow and milk production has not been studied systematically. The present review summarizes a series of key milk yield regulatory factors mediated by whole-mammary fluid flow, including milk, mammary blood flow, blood/tissue fluid-cell fluid flow and cell-alveolus fluid flow. Whole-mammary fluid flow regulates milk production by altering transporter activity, ion channels, local microcirculation-related factors, driving force of fluid transport (osmotic pressure or electrochemical gradient), cellular connection state and a cell volume sensitive mechanism. In addition, whole-mammary fluid flow plays important roles in milk synthesis and secretion. Knowledge gained from fluid flow-mediated regulatory mechanisms of the dairy mammary gland will lead to a fundamental understanding of lactation biology and will be beneficial for the improvement of dairy productivity. © 2017 Society of Chemical Industry.

Effects of dietary physical or nutritional factors on morphology of rumen papillae and transcriptome changes in lactating dairy cows based on three different forage-based diets.

BACKGROUND: Rumen epithelial tissue plays an important role in nutrient absorption and rumen health. However, whether forage quality and particle size impact the rumen epithelial morphology is unclear. The current study was conducted to elucidate the effects of forage quality and forage particle size on rumen epithelial morphology and to identify potential underlying molecular mechanisms by analyzing the transcriptome of the rumen epithelium (RE). To achieve these objectives, 18 mid-lactation dairy cows were allocated to three groups (6 cows per group), and were fed with one of three different forage-based diets, alfalfa hay (AH), corn stover (CS), and rice straw (RS) for 14 weeks, respectively. Ruminal volatile fatty acids (VFAs) and epithelial thickness were determined, and RNA-sequencing was conducted to identify the transcriptomic changes of rumen epithelial under different forage-based diets. RESULTS: The RS diet exhibited greater particle size but low quality, the AH diet was high nutritional value but small particle size, and CS diet was low quality and small particle size. The ruminal total VFA concentration was greater in AH compared with those in CS or RS. The width of the rumen papillae was greater in RS-fed cows than in cows fed AH or CS. In total, 31, 40, and 28 differentially expressed (DE, fold change > 2, FDR < 0.05) genes were identified via pair-wise comparisons including AH vs. CS, AH vs. RS, and RS vs. CS, respectively. Functional classification analysis of DE genes revealed dynamic changes in ion binding (such as DSG1) between AH and CS, proliferation and apoptotic processes (such as BAG3, HLA-DQA1, and UGT2B17) and complement activation (such as C7) between AH or RS and CS. The expression of HLA-DQA1 was down-regulated in RS compared with AH and CS, and the expression of UGT2B17 was down-regulated in RS compared with CS, with positive (R = 0.94) and negative (R = -0.96) correlation with the width of rumen epithelial papillae (P < 0.05), respectively. CONCLUSION: Our results suggest that both nutrients (VFAs) and particle sizes can alter expression of genes involved in cell proliferation/apoptosis process and complement complex. Our results suggest that particle size may be more important in regulating rumen epithelial morphology when animals are fed with low-quality forage diets and the identified DE genes may affect the RE nutrient absorption or morphology of RE. Our findings provide insights into the effects of the dietary particle size in the future management of dairy cow feeding, that when cows were fed with low-quality forage (such as rice straw), smaller particle size may be beneficial for nutrients absorption and milk production.

Metabolomics of four biofluids from dairy cows: potential biomarkers for milk production and quality.

The fundamental understanding of the mechanisms regulating milk protein synthesis is limited. This study aimed to elucidate the metabolic mechanisms of milk production affected by forage quality through studying metabolites from four biofluids (rumen fluid, milk, serum, and urine) collected from 16 lactating cows fed alfalfa hay (AH, high-quality, n = 8) and corn stover (CS, low-quality, n = 8) using gas chromatography-time-of-flight/mass spectrometry. The cows fed AH exhibited higher milk yield (P < 0.01), milk protein yield (P = 0.04), and milk efficiency (P < 0.01) than those fed CS. A total of 165, 195, 218, and 156 metabolites were identified in the rumen fluid, milk, serum, and urine, respectively, while 29 metabolites were found in all four biofluids. In addition 55, 8, 28, and 31 metabolites in each biofluid were significantly different (VIP > 1 and P < 0.05) between the AH- and CS-fed animals. These metabolites were involved in glycine, serine, and threonine metabolism; tyrosine metabolism; and phenylalanine metabolism. Further integrated key metabolic pathway analysis showed that the AH-fed cows may have more comprehensive amino acid metabolisms, suggesting that these metabolite-associated pathways may serve as biomarkers for higher milk yield and better milk protein quality.

Cross-Oxygen Gradients Transcriptomic Comparison Revealed the Central Role of MAPK and Hippo in Hypoxia-Mediated Mammary Proliferation Inhibition.

The role of hypoxia in terms of affecting mammary epithelial cells (MECs) proliferation is closely associated with the milk synthesis of lactating mammals. Primary bovine MECs were cultured at 1, 6, 11, 16, and 21% O2 for 24 h. The results showed that cell proliferation decreased linearly, and hypoxic inducible factor (HIF)-1α expression increased linearly along with the declining O2. The linear increase in oxidative stress resulted in the accumulation of malondialdehyde and reactive oxygen species and decreased antioxidant enzyme activities following the reduced O2. Concerning mitochondria, the dynamin-related protein 1 showed improved expression, and optin atrophy protein 1 decreased along with the decreasing O2 gradient, which led to decreased mitochondrial mass and mitophagy emerging under 1% O2. Oxygen concentration-trend RNA-seq analysis was conducted. Specifically, HIF-1-MAPK (1% O2), PI3K-Akt-MAPK (6% O2), and p53-Hippo (11 and 16% O2) were found to primarily regulate cell proliferation in response to hypoxia compared with normoxia (21%), respectively. In conclusion, our study suggests that bMEC proliferation is suppressed in low-oxygen conditions, and is exacerbated following the reduced oxygen supply. The cross-oxygen gradient comparisons suggest that MAPK and Hippo, which are core pathways of mammary cell proliferation, are repressed by hypoxia via oxidative-stress-dependent signals.

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.

Heat stress affects dairy cow health status through blood oxygen availability.

BACKGROUND: Rises in global warming and extreme weather occurrence make the risk of heat stress (HS) induced by high ambient temperatures more likely in high-yielding dairy cows, resulting in low milk quality and yield. In animals, oxygen is involved in many physiological and metabolic processes, but the effects of HS on oxygen metabolism remain unclear. Thus, the current study aimed to investigate how oxygen metabolism plays a role in health status of dairy cows by measuring the milk yield, milk composition, and blood biochemical variables of cows under different levels of HS: none (No-HS), mild (Mild-HS), and moderate HS (Mod-HS). RESULTS: The HS significantly increased rectal temperature (Ptreat < 0.01) and respiration rate (Ptreat < 0.01). Under Mod-HS, greater Na+ (P < 0.05) and lower total CO2, and pH (P < 0.05) were observed relative to those under No-HS and Mild-HS. Oxygen concentrations in both coccygeal artery and mammary vein (Ptreat < 0.01) were lower under Mod-HS than under No-HS. Coccygeal vein concentrations of heat shock protein 90 (HSP90) (P < 0.05) increased during Mod-HS compared with those in cows under No-HS. Malondialdehyde increased during Mod-HS, and glutathione peroxidase (P < 0.01) increased during Mild-HS. Coccygeal vein concentrations of vascular endothelial growth factor (P < 0.01), heme oxygenase-1 (P < 0.01), and hypoxia-inducible factor 1α (P < 0.01) were greater in cows under Mod-HS than those under No-HS. Red blood cell count (P < 0.01) and hemoglobin concentration (P < 0.01) were lower in the coccygeal vein of dairy cows under Mild- and Mod-HS than those of cows under No-HS. CONCLUSIONS: Exposure to HS negatively impacts the health status and lactation performance of dairy cows by limiting oxygen metabolism and transportation. However, the specific mechanism by which HS affects mammary function in cows remains unclear and requires further exploration.

Progress of Conjugated Linoleic Acid on Milk Fat Metabolism in Ruminants and Humans.

As a valuable nutrient in milk, fat accounts for a significant proportion of the energy requirements of ruminants and is largely responsible for determining milk quality. Fatty acids (FAs) are a pivotal component of milk fat. Conjugated linoleic acid (CLA) is one of the naturally occurring FAs prevalent in ruminant dairy products and meat. Increasing attention has been given to CLA because of its anti-cancer, anti-inflammatory, immune regulation, and lipid metabolism regulation properties, and these benefits potentially contribute to the growth and health of infants. In breast milk, CLA is present in trace amounts, mainly in the form of cis-9, trans-11 CLA. Notably, cis-9, trans-11 CLA improves the milk fat rate while trans-10, cis-12 CLA inhibits it. Apart from having multiple physiological functions, CLA is also a pivotal factor in determining the milk quality of ruminants, especially milk fat rate. In response to growing interest in green and healthy functional foods, more and more researchers are exploring the potential of CLA to improve the production performance of animals and the nutritional value of livestock products. Taken together, it is novel and worthwhile to investigate how CLA regulates milk fat synthesis. It is the purpose of this review to clarify the necessity for studying CLA in ruminant milk fat and breast milk fat.

Transformation of Lung Squamous Cell Carcinoma to Small Cell Lung Cancer After Immunotherapy Resistance: A Case Report.

The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following treatment with epidermal growth factor (EGFR) receptor tyrosine kinase inhibitors (TKIs) is a relatively common phenomenon. However, transformation of non-small cell lung cancer (NSCLC) to SCLC following treatment with immunotherapy is very rare. Here, we report a case of a 56-year-old patient diagnosed with driver gene mutation-negative lung squamous cell carcinoma (SCC). He received four cycles of immunotherapy with sugemalimab and chemotherapy with albumin paclitaxel in combination with carboplatin, and a partial response was achieved. Subsequently, the patient received 5 cycles of immunotherapy with sugemalimab. However, he developed rapid progression of mediastinal lymph nodes, and biopsy results showed transformation to SCLC. His tumor did not respond to the next line of carboplatin combined with etoposide, and he died six months after the discovery of SCLC transformation. In conclusion, SCLC transformation is also an important resistance mechanism for lung SCC patients treated with immunotherapy and predicts a very poor outcome. Repeat biopsy is needed for advanced lung SCC that has progressed with immunotherapy.

Antioxidant hepatic lipid metabolism can be promoted by orally administered inorganic nanoparticles.

Accumulation of inorganic nanoparticles in living organisms can cause an increase in cellular reactive oxygen species (ROS) in a dose-dependent manner. Low doses of nanoparticles have shown possibilities to induce moderate ROS increases and lead to adaptive responses of biological systems, but beneficial effects of such responses on metabolic health remain elusive. Here, we report that repeated oral administrations of various inorganic nanoparticles, including TiO2, Au, and NaYF4 nanoparticles at low doses, can promote lipid degradation and alleviate steatosis in the liver of male mice. We show that low-level uptake of nanoparticles evokes an unusual antioxidant response in hepatocytes by promoting Ces2h expression and consequently enhancing ester hydrolysis. This process can be implemented to treat specific hepatic metabolic disorders, such as fatty liver in both genetic and high-fat-diet obese mice without causing observed adverse effects. Our results demonstrate that low-dose nanoparticle administration may serve as a promising treatment for metabolic regulation.

Constraints on the utilization of cereal straw in lactating dairy cows: A review from the perspective of systems biology.

Cereal straw, a human inedible crop byproduct, can be used as a roughage source in ruminants. However, the nutrition density and palatability are very low, limiting its efficient utilization in animal production. This review aims to systematically provide an overview of the limitations of cereal straws, which is crucial for developing new strategies to enhance the efficient use of cereal straws by lactating dairy cows. Evolutionary molecular biology makes it possible to comprehensively understand the limitations of using cereal straw as a roughage source in dairy cows by different techniques, e.g., multi-omics. Main constraints for utilization of cereal straw and stover in lactating dairy cows include low contents of easily fermented carbohydrates (pectin) and essential amino acids (Met, Phe, and branched-chain amino acids), high content of lignin and silica, and low nutrient digestibility. These cause insufficient supply of the precursors for milk synthesis and result in increased loss of nutrients in feces and urine. Several molecular mechanisms are revealed by multi-omics techniques, including changed amino acid and glucose metabolism, altered rumen microbial composition and function, and differential expression of miRNAs, mRNA, and protein in multi-organs that are associated with milk synthesis. These can be targets of approaches to improve the utilization of cereal straw by dairy cows. In addition, much attention should be given to the efficient countermeasures, including pretreatments by fibrolytic enzymes or steam explosion, dietary formulations such as supplement of pectin, methionine, and branched-chain amino acids, and feeding with other functional feedstuffs, which may improve the feeding and economic value of cereal straw for lactating dairy cows. The newly revealed functional genes (such as BAG3 in the rumen, PC in the liver, CSN1S2 in the mammary gland) and biomarkers (hippuric acid) as well as the integrative signaling and metabolic pathways (phenylalanine metabolism) related to the shortages of cereal straws could be used as nutritional or genetic regulatory targets to improve dairy cow production.

Multiple-Vessel-Based Blood Gas Profiles Analysis Revealed the Potential of Blood Oxygen in Mammary Vein as Indicator of Mammary Gland Health Risk of High-Yielding Dairy Cows.

The blood gas profile is a routine method in the rapid disease diagnosis of farm animals, yet its potential in evaluating mammary health status of dairy cows remains to be investigated. This study was conducted to learn the potential of the blood gas parameter regarding the mammary gland health status in lactating dairy cows. Twenty animals were divided into two groups, the H-SCC group (milk SCC > 122 k/mL) and L-SCC group (milk SCC < 73.8 k/mL), to compare blood gas profiles from different blood vessels and to identify the key parameters associated with milk somatic cell count. H-SCC cows are higher in malondialdehyde content, but lower in SOD and T-AOC activities in the milk, compared to the L-SCC group. In terms of blood gas parameters, most differ across the three vessels, including K+, CO2 pressure, O2 pressure, HCO3−, base excess in the extracellular fluid compartment, and saturation of O2. The Pearson correlation analysis showed that oxygen-related variables in the mammary vein, including oxygen concentrations, O2 pressure, and saturation of O2, are negatively correlated with levels of malondialdehyde, lactate dehydrogenase, and plasmin in the milk. Our study revealed that oxygen-related variables in the mammary vein can be a marker in suggesting mammary-gland health status in high-yielding cows.