Maternal and infant microbiome: next-generation indicators and targets for intergenerational health and nutrition care.

Microbes are commonly sensitive to shifts in the physiological and pathological state of their hosts, including mothers and babies. From this perspective, the microbiome may be a good indicator for diseases during pregnancy and has the potential to be used for perinatal health monitoring. This is embodied in the application of microbiome from multi body sites for auxiliary diagnosis, early prediction, prolonged monitoring, and retrospective diagnosis of pregnancy and infant complications, as well as nutrition management and health products developments of mothers and babies. Here we summarized the progress in these areas and explained that the microbiome of different body sites is sensitive to different diseases and their microbial biomarkers may overlap between each other, thus we need to make a diagnosis prudently for those diseases. Based on the microbiome variances and additional anthropometric and physical data, individualized responses of mothers and neonates to meals and probiotics/prebiotics were predictable, which is of importance for precise nutrition and probiotics/prebiotics managements and developments. Although a great deal of encouraging performance was manifested in previous studies, the efficacy could be further improved by combining multi-aspect data such as multi-omics and time series analysis in the future. This review reconceptualizes maternal and infant health from a microbiome perspective, and the knowledge in it may inspire the development of new options for the prevention and treatment of adverse pregnancy outcomes and bring a leap forward in perinatal health care.

Clinical study of occult fractures around the prosthesis in primary total hip arthroplasty.

Objective To determine the prevalence, prevention measures, and risk factors for occult periprosthetic fractures after primary total hip arthroplasty (THA), as well as to determine whether or not they are the root of early THA failure. Methods From January 2014 to December 2018, 755 patients (769 hips) underwent primary total hip arthroplasty were retrospectively analyzed, including 327 males (339 hips) and 428 females (430 hips). X-ray, CT and 3D reconstruction of hip were performed before and after operation. By using CT to diagnose the occult fractures, the patients were then monitored and evaluated. Age, sex, body mass index (BMI), preoperative diagnosis, osteoporosis, kind of prosthesis, and the surgeon's experience should all be considered. Patients with occult fracture were followed up, the fracture healing and prosthesis stability were recorded and analyzed. Results There are 23 of 769 cases (23/769) had occult fracture around the prosthesis, with an incidence of 2.99% (23/769);. The total revision rate was 0.52% (4/769). The revision patients accounted for 17.39% (4/23) of the patients with occult femoral fractures. The remaining patients received conservative care and successfully joined without their prostheses slipping. Osteoporosis, body mass index, and the surgeon's experience were identified as the risk variables for periprosthetic occult fractures by univariate analysis (P < 0.05). Conclusion Periprosthetic occult fracture was a complication that can not be ignored in primary total hip arthroplasty. It is the cause of early failure of prosthesis. Osteoporosis, BMI and the surgeon's experience are all risk factors for periprosthetic occult fractures.

Mitochondrial genomic analyses provide new insights into the "missing" atp8 and adaptive evolution of Mytilidae.

BACKGROUND: Mytilidae, also known as marine mussels, are widely distributed in the oceans worldwide. Members of Mytilidae show a tremendous range of ecological adaptions, from the species distributed in freshwater to those that inhabit in deep-sea. Mitochondria play an important role in energy metabolism, which might contribute to the adaptation of Mytilidae to different environments. In addition, some bivalve species are thought to lack the mitochondrial protein-coding gene ATP synthase F0 subunit 8. Increasing studies indicated that the absence of atp8 may be caused by annotation difficulties for atp8 gene is characterized by highly divergent, variable length. RESULTS: In this study, the complete mitochondrial genomes of three marine mussels (Xenostrobus securis, Bathymodiolus puteoserpentis, Gigantidas vrijenhoeki) were newly assembled, with the lengths of 14,972 bp, 20,482, and 17,786 bp, respectively. We annotated atp8 in the sequences that we assembled and the sequences lacking atp8. The newly annotated atp8 sequences all have one predicted transmembrane domain, a similar hydropathy profile, as well as the C-terminal region with positively charged amino acids. Furthermore, we reconstructed the phylogenetic trees and performed positive selection analysis. The results showed that the deep-sea bathymodiolines experienced more relaxed evolutionary constraints. And signatures of positive selection were detected in nad4 of Limnoperna fortunei, which may contribute to the survival and/or thriving of this species in freshwater. CONCLUSIONS: Our analysis supported that atp8 may not be missing in the Mytilidae. And our results provided evidence that the mitochondrial genes may contribute to the adaptation of Mytilidae to different environments.

Heat stress impacts the multi-domain ruminal microbiota and some of the functional features independent of its effect on feed intake in lactating dairy cows.

BACKGROUND: Heat stress (HS) affects the ruminal microbiota and decreases the lactation performance of dairy cows. Because HS decreases feed intake, the results of previous studies were confounded by the effect of HS on feed intake. This study examined the direct effect of HS on the ruminal microbiota using lactating Holstein cows that were pair-fed and housed in environmental chambers in a 2 × 2 crossover design. The cows were pair-fed the same amount of identical total mixed ration to eliminate the effect of feed or feed intake. The composition and structure of the microbiota of prokaryotes, fungi, and protozoa were analyzed using metataxonomics and compared between two thermal conditions: pair-fed thermoneutrality (PFTN, thermal humidity index: 65.5) and HS (87.2 for daytime and 81.8 for nighttime). RESULTS: The HS conditions altered the structure of the prokaryotic microbiota and the protozoal microbiota, but not the fungal microbiota. Heat stress significantly increased the relative abundance of Bacteroidetes (primarily Gram-negative bacteria) while decreasing that of Firmicutes (primarily Gram-positive bacteria) and the Firmicutes-to-Bacteroidetes ratio. Some genera were exclusively found in the heat-stressed cows and thermal control cows. Some co-occurrence and mutual exclusion between some genera were also found exclusively for each thermal condition. Heat stress did not significantly affect the overall functional features predicted using the 16S rRNA gene sequences and ITS1 sequences, but some enzyme-coding genes altered their relative abundance in response to HS. CONCLUSIONS: Overall, HS affected the prokaryotes, fungi, and protozoa of the ruminal microbiota in lactating Holstein cows to a different extent, but the effect on the structure of ruminal microbiota and functional profiles was limited when not confounded by the effect on feed intake. However, some genera and co-occurrence were exclusively found in the rumen of heat-stressed cows. These effects should be attributed to the direct effect of heat stress on the host metabolism, physiology, and behavior. Some of the "heat-stress resistant" microbes may be useful as potential probiotics for cows under heat stress.

Functional Properties of Cancer Epithelium and Stroma-Derived Exosomes in Head and Neck Squamous Cell Carcinoma.

Stroma-cancer cell crosstalk involves a complex signaling network that contributes to tumor progression, including carcinogenesis, angiogenesis, migration, invasion, and therapy resistance in cancers. Exosomes, as extracellular membranous nanovesicles released by almost all types of cells, including tumor cells and stromal cells, play a critical role in signal delivery and material communication, in which the characteristics of their parent cells are reflected. The tumor or stroma-derived exosomes mediate cell-cell communication in the tumor microenvironment by transporting DNA, RNA, proteins, lipids, and metabolites. Recent studies on head and neck squamous cell carcinoma (HNSCC) have demonstrated that tumor-derived exosomes support various tumor biological behaviors, whereas the functional roles of stroma-derived exosomes remain largely unknown. Although these exosomes are emerging as promising targets in early diagnosis, prognostic prediction, and pharmaceutical carriers for antitumor therapy, there are still multiple hurdles to be overcome before they can be used in clinical applications. Herein, we systematically summarize the promotive roles of the epithelium and stroma-derived exosomes in HNSCC and highlight the potential clinical applications of exosomes in the treatment of HNSCC.

Direct effect of lipopolysaccharide and histamine on permeability of the rumen epithelium of steers ex vivo.

Disruption of the ruminal epithelium barrier occurs during subacute ruminal acidosis due to low pH, hyper-osmolality, and increased concentrations of lipopolysaccharide and histamine in ruminal fluid. However, the individual roles of lipopolysaccharide and histamine in the process of ruminal epithelium barriers disruption are not clear. The objective of the present investigation was to evaluate the direct effect of lipopolysaccharide and histamine on the barrier function of the ruminal epithelium. Compared with control (CON), histamine (HIS, 20 µM) increased the short-circuit current (Isc; 88.2%, P < 0.01), transepithelial conductance (Gt; 29.7%, P = 0.056), and the permeability of fluorescein 5(6)-isothiocyanate (FITC) (1.04-fold, P < 0.01) of ruminal epithelium. The apparent permeability of LPS was 1.81-fold higher than HIS (P < 0.01). The mRNA abundance of OCLN in ruminal epithelium was decreased by HIS (1.1-fold, P = 0.047). The results of the present study suggested that mucosal histamine plays a direct role in the disruption of ruminal epithelium barrier function, whereas lipopolysaccharide (at a pH of 7.4) has no effect on the permeability of rumen tissues ex vivo.

Lipopolysaccharide and histamine are common chemicals in rumen when the ruminant animal takes too much concentrate. We wandered whether these two chemicals have direct effects on the rumen tissues. Using Ussing chamber, we found that histamine could directly improve the permeability of rumen barrier.

Fundamental and Clinical Applications of Materials Based on Cancer-Associated Fibroblasts in Cancers.

Cancer stromal cells play a role in promoting tumor relapse and therapeutic resistance. Therefore, the current treatment paradigms for cancers are usually insufficient to eradicate cancer cells, and anti-cancer therapeutic strategies targeting stromal cells have been developed. Cancer-associated fibroblasts (CAFs) are perpetually activated fibroblasts in the tumor stroma. CAFs are the most abundant and highly heterogeneous stromal cells, and they are critically involved in cancer occurrence and progression. These effects are due to their various roles in the remodeling of the extracellular matrix, maintenance of cancer stemness, modulation of tumor metabolism, and promotion of therapy resistance. Recently, biomaterials and nanomaterials based on CAFs have been increasingly developed to perform gene or protein expression analysis, three-dimensional (3D) co-cultivation, and targeted drug delivery in cancer treatment. In this review, we systematically summarize the current research to fully understand the relevant materials and their functional diversity in CAFs, and we highlight the potential clinical applications of CAFs-oriented biomaterials and nanomaterials in anti-cancer therapy.

Assessment of veterinary antibiotics from animal manure-amended soil to growing alfalfa, alfalfa silage, and milk.

Using animal manure as organic fertilizer to grow fodder crops is causing public health concerns because animal manure is the major reservoir of veterinary antibiotics. In this study, we used a mathematical model to estimate the risk of human exposure to veterinary antibiotics when using swine manure as organic fertilizer to grow alfalfa (Medicago sativa L.). Alfalfa was planted in a greenhouse and fertilized with swine manure spiked with oxytetracycline (OTC, at 0, 150, and 1500 mg/kg of manure), ofloxacin (OFL, at 0, 15, and 150 mg/kg), or sulfamonomethoxine (SMM, at 0, 5, 15 and 150 mg/kg). Alfalfa was harvested at the budding stage and ensiled for 60 days. Results showed that OTC and OFL could be detected in the alfalfa root, stem, and leaf with a concentration ranging from 8.85 to 59.17 µg OTC /kg and from 1.50 to 4.10 µg OFL/kg dry matter, but SMM could only be detected in the root ranging from 29.10 to 63.75 µg/kg dry matter. The ensiling for 60 days decreased the OFL concentration by 68.7% but only slightly decreased the OTC concentration. The maximum daily exposures of humans to OTC and OFL through liquid milk consumption were estimated to be 5.84E-8 and 1.63E-8 µg, respectively, both of which are well below the intake levels of OTC (72 µg) and OFL (54 µg) mandated by the European Union. The results of the present study indicate that using swine manure as organic fertilizer to grow alfalfa poses a limited risk for human exposure to veterinary antibiotics through the consumption of liquid milk.

Impacts of Heat Stress-Induced Oxidative Stress on the Milk Protein Biosynthesis of Dairy Cows.

Heat stress (HS) is one of the most important factors posing harm to the economic wellbeing of dairy industries, as it reduces milk yield as well as milk protein content. Recent studies suggest that HS participates in the induction of tissue oxidative stress (OS), as elevated levels of reactive oxygen species (ROS) and mitochondrial dysfunction were observed in dairy cows exposed to hot conditions. The OS induced by HS likely contributes to the reduction in milk protein content, since insulin resistance and apoptosis are promoted by OS and are negatively associated with the synthesis of milk proteins. The apoptosis in the mammary gland directly decreases the amount of mammary epithelial cells, while the insulin resistance affects the regulation of insulin on mTOR pathways. To alleviate OS damages, strategies including antioxidants supplementation have been adopted, but caution needs to be applied as an inappropriate supplement with antioxidants can be harmful. Furthermore, the complete mechanisms by which HS induces OS and OS influences milk protein synthesis are still unclear and further investigation is needed.

The hypothesis of tumor-associated macrophages mediating semi-phagocytosis of cancer cells in distant metastasis.

Tweetable abstract Tumor-associated macrophages might promote the distant metastasis of tumor cells by semi-phagocytosis. The authors propose that this newly discovered process occurs in tumor-associated macrophages and may lead to a novel approach for blocking cancer metastasis.

Supplementation with sodium butyrate improves growth and antioxidant function in dairy calves before weaning.

BACKGROUND: There is increasing research interest in using short-chain fatty acids (SCFAs) including butyrate as potential alternatives to antibiotic growth promoters in animal production. This study was conducted to evaluate the effects of supplementation of sodium butyrate (SB) in liquid feeds (milk, milk replacer, and the mixture of both) on the growth performance, rumen fermentation, and serum antioxidant capacity and immunoglobins in dairy calves before weaning. Forty healthy female Holstein calves (4-day-old, 40 ± 5 kg of body weight) were housed in individual hutches and randomly allocated to 1 of 4 treatment groups (n = 10 per group) using the RAND function in Excel. The control group was fed no SB (SB0), while the other three groups were supplemented with 15 (SB15), 30 (SB30), or 45 (SB45) g/d of SB mixed into liquid feeds offered. The calves were initially fed milk only (days 2 to 20), then a mixture of milk and milk replacer (days 21 to 23), and finally milk replacer only (days 24 to 60). RESULTS: The SB supplementation enhanced growth and improved feed conversion into body weight gain compared with the SB0 group, and the average daily gain increased quadratically with increasing SB supplementation. No significant effect on rumen pH; concentrations of NH3-N, individual and total VFAs; or acetate: propionate (A:P) ratio was found during the whole experimental period. Serum glutathione peroxidase activity increased linearly with the increased SB supplementation, while the serum concentration of maleic dialdehyde linearly decreased. Serum concentrations of immunoglobulin A, immunoglobulin G, or immunoglobulin M were not affected by the SB supplementation during the whole experimental period. CONCLUSIONS: Under the conditions of this study, SB supplementation improved growth performance and antioxidant function in pre-weaned dairy calves. We recommended 45 g/d as the optimal level of SB supplementation mixed into liquid feeds (milk or milk replacer) to improve the growth and antioxidant function of dairy calves before weaning.

Effects of Heat Stress on the Ruminal Epithelial Barrier of Dairy Cows Revealed by Micromorphological Observation and Transcriptomic Analysis.

Heat stress (HS) alters the rumen fermentation of dairy cows thereby affecting the metabolism of rumen papillae and thus the epithelial barrier function. The aim of the present study was to investigate if HS damages the barrier function of ruminal epithelia. Eight multiparous Holstein dairy cows with rumen cannula were randomly equally allocated to two replicates (n = 4), with each replicate being subjected to heat stress or thermal neutrality and pair-feeding in four environmental chambers. Micromorphological observation showed HS aggravated the shedding of the corneum and destroyed the physical barrier of the ruminal epithelium to a certain extent. Transcriptomics analysis of the rumen papillae revealed pathways associated with DNA replication and repair and amino acid metabolism were perturbated, the biological processes including sister chromatid segregation, etc. were up-regulated by HS, while the MAPK and NF-kB cell signaling pathways were downregulated. However, no heat stress-specific change in the expression of tight junction protein or TLR4 signaling was found, suggesting that HS negatively affected the physical barrier of the ruminal epithelium to some extent but did not break the ruminal epithelium. Heat stress invoked mechanisms to maintain the integrity of the rumen epithelial barrier by upregulating the expression of heat shock protein and repairments in rumen papillae. The increase in amino acid metabolism in rumen papillae might affect the nutrient utilization of the whole body. The findings of this study may inform future research to better understand how heat stress affects the physiology and productivity of lactating cows and the development of mitigation strategies.

Diet Composition Affects Liver and Mammary Tissue Transcriptome in Primiparous Holstein Dairy Cows.

The objective of the present study was to evaluate the overall adaptations of liver and mammary tissue to a corn stover (CS) compared to a mixed forage (MF) diet in mid-lactation primiparous dairy cows. Twenty-four primiparous lactating Holstein cows were randomly allocated to 2 groups receiving either an alfalfa forage diet (MF, F:C = 60:40) with Chinese wildrye, alfalfa hay and corn silage as forage source or a corn stover forage diet (CS, F:C = 40:60). A subgroup of cows (n = 5/diet) was used for analysis of liver and mammary transcriptome using a 4 × 44K Bovine Agilent microarray chip. The results of functional annotation analysis showed that in liver CS vs. MF inhibited pathways related to lipid metabolism while induced the activity of the potassium channel. In mammary tissue, fatty acid metabolism was activated in CS vs. MF. In conclusion, the analysis of genes affected by CS vs. MF indicated mammary gland responding to lower level of linoleate from the diet (lower in CS vs. MF) by activating the associated biosynthesis metabolic pathway while the liver adaptively activated potassium transport to compensate for a lower K ingestion.

Nutrient value of wild fodder species and the implications for improving the diet of mithun (Bos frontalis) in Dulongjiang area, Yunnan Province, China.

Wild fodder plants are valuable because they provide an important livestock feed resource globally, especially for smallholder farmers, and have important roles in natural resource management. In-depth knowledge of wild forage plants can motivate local people for feed resource and habitat conservation of threatened herbivores such as Mithun (Bos frontalis). Mithun occur in small patches in the mountains of Dulongjiang, nearby villagers domesticated this animal but left animal to freely graze in the mountains. Many fodder plants occur in these mountains, however, little is known about their nutritional value. We conducted an ethnobotanical survey to document important wild fodder plants consumed by mithun in the Dulongjiang Township. The nutritional content of 21 highly mentioned wild fodder plants in an ethnobotanical survey was examined. Laboratory analysis showed that Fagopyrum dibotrys were the fodder species with the highest crude protein (CP) content (26.89%), followed by Polygonum molle (21.88%) and Hydrangea longipes (21.12%). Synthesis of relative feed value index and grey relational grade, P. molle, H. longipes and Tetrastigma obtectum were ranked the top three nutritional fodders. There was a significant difference between 21 species on their in vitro digestibility and the most highly digestible fodder species was Elatostema hookerianum. Linear model analysis on relationship between frequency of citation of 21 wild forage plants by local farmers and their nutrient composition showed that the frequency was significantly positively correlated with the nutritional value of the feed (R2 = 0.28, P < 0.05). We concluded that these species have high nutritional values to improve mithun production in integrated crop-livestock systems. Fodder species or mixtures of species with useful nutritional characters could be cultivated to improve livestock productivity, habitat conservation including that of mithun and wild forage resource management.

Heat stress induces proteomic changes in the liver and mammary tissue of dairy cows independent of feed intake: An iTRAQ study.

Heat stress decreases milk yield and deleteriously alters milk composition. Reduced feed intake partially explains some of the consequences of heat stress, but metabolic changes in the mammary tissue and liver associated with milk synthesis have not been thoroughly evaluated. In the current study, changes of protein abundance in the mammary tissue and liver between heat-stressed cows with ad libitum intake and pair-fed thermal neutral cows were investigated using the iTRAQ proteomic approach. Most of the differentially expressed proteins from mammary tissue and liver between heat-stressed and pair-fed cows were involved in Gene Ontology category of protein metabolic process. Pathway analysis indicated that differentially expressed proteins in the mammary tissue were related to pyruvate, glyoxylate and dicarboxylate metabolism pathways, while those in the liver participated in oxidative phosphorylation and antigen processing and presentation pathways. Several heat shock proteins directly interact with each other and were considered as central "hubs" in the protein interaction network. These findings provide new insights to understand the turnover of protein biosynthesis pathways within hepatic and mammary tissue that likely contribute to changes in milk composition from heat-stressed cows.

Blood amino acids profile responding to heat stress in dairy cows.

OBJECTIVE: The objective of this experiment was to investigate the effects of heat stress on milk protein and blood amino acid profile in dairy cows. METHODS: Twelve dairy cows with the similar parity, days in milk and milk yield were randomly divided into two groups with six cows raised in summer and others in autumn, respectively. Constant managerial conditions and diets were maintained during the experiment. Measurements and samples for heat stress and no heat stress were obtained according to the physical alterations of the temperature-humidity index. RESULTS: Results showed that heat stress significantly reduced the milk protein content (p<0.05). Heat stress tended to decrease milk yield (p = 0.09). Furthermore, heat stress decreased dry matter intake, the concentration of blood glucose and insulin, and glutathione peroxidase activity, while increased levels of non-esterified fatty acid and malondialdehyde (p<0.05). Additionally, the concentrations of blood Thr involved in immune response were increased under heat stress (p<0.05). The concentration of blood Ala, Glu, Asp, and Gly, associated with gluconeogenesis, were also increased under heat stress (p<0.05). However, the concentration of blood Lys that promotes milk protein synthesis was decreased under heat stress (p<0.05). CONCLUSION: In conclusion, this study revealed that more amino acids were required for maintenance but not for milk protein synthesis under heat stress, and the decreased availability of amino acids for milk protein synthesis may be attributed to competition of immune response and gluconeogenesis.