Mechanisms of Corticosteroid Resistance in Type 17 Asthma.

IL-17A plays an important role in the pathogenesis of asthma, particularly the neutrophilic corticosteroid (CS)-resistant subtype of asthma. Clinical studies suggest that a subset of asthma patients, i.e., Th17/IL-17A-mediated (type 17) CS-resistant neutrophilic asthma, may improve with Th17/IL-17A pathway blockade. However, little is known about the mechanisms underlying type 17 asthma and CS response. In this article, we show that blood levels of lipocalin-2 (LCN2) and serum amyloid A (SAA) levels are positively correlated with IL-17A levels and are not inhibited by high-dose CS usage in asthma patients. In airway cell culture systems, IL-17A induces these two secreted proteins, and their induction is enhanced by CS. Furthermore, plasma LCN2 and SAA levels are increased in mice on a preclinical type 17 asthma model, correlated to IL-17A levels, and are not reduced by glucocorticoid (GC). In the mechanistic studies, we identify CEBPB as the critical transcription factor responsible for the synergistic induction of LCN2 and SAA by IL-17A and GC. IL-17A and GC collaboratively regulate CEBPB at both transcriptional and posttranscriptional levels. The posttranscriptional regulation of CEBPB is mediated in part by Act1, the adaptor and RNA binding protein in IL-17A signaling, which directly binds CEBPB mRNA and inhibits its degradation. Overall, our findings suggest that blood LCN2 and SAA levels may be associated with a type 17 asthma subtype and provide insight into the molecular mechanism of the IL-17A-Act1/CEBPB axis on these CS-resistant genes.

A dynamic individual yak heifer live body weight estimation method using the YOLOv8 network and body parameter detection algorithm.

Live body weight (LBW) is one of the most important parameters for supervising the growth and development of livestock. The yak (Bos grunniens) is a special species of cattle that lives on the Qinghai-Tibetan Plateau. Yaks are more untamed than regular cattle breeds, thus it is more challenging to measure their LBW. In this study, a YOLOv8 yak detection and LBW estimation models were used to automatically estimate yak LBW in real-time. First, the proper posture (normal posture) and individual yak identification was confirmed and then the YOLOv8 detection model was used for LBW estimation from 2-dimensional (2D) images. Yak LBW was estimated through yak body parameter extraction and a simple linear regression between the estimated yak LBW and the actual measured yak LBW. The results showed that the overall detection performance of yak normal yak posture was described by precision, recall, and mean Average Precision 50 (mAP50) indicators, reaching 81.8, 86.0, and 90.6%, respectively. The best yak identification results were represented by precision, recall, and mAP50 values of 97.8, 96.4, and 99.0%, respectively. The yak LBW estimation model achieved better results for the 12 mo old yaks with shorter hair with R2, root mean square error (RMSE), mean absolute percentage error (MAPE), and Multiple R values of 0.96, 2.43 kg, 1.69%, and 0.98, respectively. The results demonstrate that yak LBW can be estimated and monitored in real-time using this approach. This study has the potential to be used for daily yak LBW monitoring in an unstressed manner and to save considerable labor resources for large-scale livestock farms. In the future, to reduce the limitations caused by the impacts of yak hair and light condition data sets of dairy cows and yaks of different ages will be used to improve and generalize the model.

Unlocking the potential of milk whey protein components in colorectal cancer prevention and therapy.

Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have protective effects, reducing the risk of colorectal cancer. Most of the literature has explored the potential role of milk minerals and vitamins in managing colorectal cancer. Yet, there is a paucity of a comprehensive summary of the anticancer attributes of milk protein components and their underlying mechanisms of action. Recent advancements have spotlighted the potential of whey proteins, including ß-lactoglobulin, α-lactalbumin, serum albumin, and lactoferrin, as promising candidates for both the prevention and treatment of colorectal cancer. Notably, whey proteins have demonstrated a more pronounced capacity for suppressing carcinogen-induced tumors when compared to casein. Their strong binding affinity enables them to serve as effective carriers for small molecules or drugs targeting colon cancer therapy. Furthermore, numerous studies have underscored the anti-inflammatory and antioxidant prowess of whey proteins in cancer prevention. Additionally, whey proteins have been shown to trigger apoptosis, hinder tumor cell proliferation, and impede metastasis. This comprehensive review, therefore, not only substantiates the significance of incorporating whey protein components into a balanced daily diet but also underscores their potential in safeguarding against the onset and progression of colorectal cancer.

Dairy products have consistently had protective effects in reducing the risk of colorectal cancer.Whey proteins have shown promise as candidates for the prevention and treatment of colorectal cancer.Whey proteins have a strong binding ability, enabling them to act as carriers of small molecules or drugs targeting colon cancer therapy.Their anti-inflammatory and anti-oxidant capacity may play a role in cancer prevention.Whey proteins could induce apoptosis and inhibit the proliferation and metastasis of tumor cells.

Validation of a methodology for characterization of rumination, lying, standing, and performing non-nutritive oral behaviors and behavioral patterns in Holstein dairy calves.

Calf behavior is closely related to its early growth, production performance, and health performance. Continuous behavior recording is the most accurate but also time-consuming method used for monitoring animal behaviors, so the instantaneous sampling method is often adopted to minimize the time required to quantify behavioral observations in animal studies. Moreover, the optimal sampling intervals required to yield accurate information for estimating Holstein dairy calves' behaviors are still unknown. Our primary objective was to determine the most optimal sampling intervals for monitoring behaviors of Holstein dairy calves during preweaning and weaning periods to improve efficiency while maintaining reliability. The secondary objective was to describe their behavioral patterns. Rumination, lying, standing, and non-nutritive oral behavior (NNOB) data of 18 calves (observation time: 360 h/calf, 6,480 h in total) were continuously recorded for 15 d (3 d at 1, 3, 6, 9, and 12 wk of age). The continuous behavioral data were compared with instantaneous sampling at 5 s, 10 s, 15 s, 30 s,1 min, 3 min, 5 min, 10 min, 15 min, 30 min, and 60 min intervals. Sampling intervals were considered accurate if they met 4 criteria: coefficient of determination ≥0.90 (i.e., strongly related to true values), slope = 1, intercept = 0 (i.e., they did not over- or underestimate true values), and relative error <10%. The most optimal sampling interval was considered the highest sampling interval among the 11 sampling intervals that meet the criteria for accurate monitoring. As expected, the strength of the linear relationship between the continuous recording and instantaneous sampling decreased as the sampling intervals increased. The results varied across the different behaviors, with rumination, lying, standing, and NNOB being reliable at instantaneous recordings of 3 min, 10 min, 10 min, and 1 min for the preweaning period (1, 3, and 6 wk of age) and 10 min, 10 min, 15 min, and 3 min for the postweaning period (9 and 12 wk of age). In terms of behavioral patterns, lying time decreased, whereas rumination, standing, and NNOB time increased with age. After weaning, no significant changes in time spent performing these behaviors. Additionally, the rumination behavioral pattern becomes stable after wk 6 with decreasing after the morning feeding and occurring mainly in the morning. In conclusion, instantaneous sampling is a reliable method for monitoring the behaviors of dairy calves, but the optimal sampling intervals should be selected based on different ages and management conditions.

Different feed presentations affect subsequent feed sorting and rumen pH for a short period in weaned calves.

The objective of this study was to investigate the short- and long-term effects of different feed presentations on feed sorting and rumen pH in weaned calves. Thirty-six weaned female calves at the age of 12 wk (78 d) were raised in pairs (18 pens; n = 6/treatment) and randomly exposed to 1 of 3 feed presentation treatments: (1) concentrate ration (CON, only exposed to concentrate); (2) separate ration (CH, exposed to concentrate and hay as separate components); and (3) mixed ration (Mix, exposed to a mixed diet containing 75% concentrate and 25% hay). After 4 wk (from d 78 to 105) on different feed presentations, all weaned calves were introduced to a novel total mixed ration (TMR) for another 12 wk (from d 106 to 189). Fresh feed and orts were sampled daily before (wk 12 to 15) and after (wk 16, 17, and 28) transitioning to a TMR diet for analysis of feed sorting. Rumen fluid was sampled in wk 12, 13, 15, 16, 17, and 28 to determine rumen pH. The performance of weaned calves was affected by the different feed presentations during the pre-changing period, such that calves fed CON had a lower dry matter intake (DMI) and average daily gain than calves fed CH and Mix diets. When calves were introduced to the Mix diet, they immediately developed a higher degree of sorting behavior against the long particle fractions. Upon transition to TMR, we did not observe any differences in the performance of calves. However, the sorting behavior established in Mix calves persisted and was similar to calves previously fed the CON diet, whereas the extent of feed sorting in calves initially fed CH was less compared with that in the other 2 treatments in wk 16 and 17. Before changing the diet was transitioned to a TMR, calves fed CON had a lower rumen pH than calves fed CH and Mix. Although rumen pH in all treatments increased to the same level after the diet changed, we observed a tendency toward lower rumen pH in calves fed Mix compared with calves fed CH at wk 17, which might have resulted from the higher degree of feed sorting in these calves. However, by the end of the experiment (wk 28), feed sorting and rumen pH were similar across all treatments. These results indicated a short-term effect of previous feed presentations on subsequent feed sorting and rumen pH, but in the long term disappeared.

Balloon catheter dilation technology combined with a fibrolaryngoscope to treat a maxillary sinus cyst.

A prospective randomized controlled study was conducted to investigate the effect of balloon catheter dilation technology combined with a fibrolaryngoscope in the treatment of a maxillary sinus cyst. The clinical data of 14 cases (19 maxillary sinuses) with balloon catheter dilation technology combined with a fibrolaryngoscope to remove sinus cysts (balloon group) and 16 cases (23 maxillary sinuses) with conventional nasal endoscopic sinus surgery to remove sinus cysts (conventional group) were analyzed. All cases have completed the preoperative and postoperative SNOT-20, nasal endoscopy and coronal sinus CT scan. Lund-Kennedy endoscopic and Lund-Mackay CT scan staging scores were recorded. All patients were followed up for 24 weeks after the operation. The SNOT-20 scores, Lund-Kennedy endoscopic and Lund-Mackay CT scan staging scores were lower in the balloon group than that in the control group. Balloon catheter dilation technology combined with a fibrolaryngoscope can effectively preserve the function and structures of the nasal cavity and sinus, making it a good choice in the treatment of a retention cyst of the maxillary sinus.

METnet: A novel deep learning model predicting MET dysregulation in non-small-cell lung cancer on computed tomography images.

BACKGROUND: Mesenchymal epithelial transformation (MET) is a key molecular target for diagnosis and treatment of non-small cell lung cancer (NSCLC). The corresponding molecularly targeted therapeutics have been approved by Food and Drug Administration (FDA), achieving promising results. However, current detection of MET dysregulation requires biopsy and gene sequencing, which is invasive, time-consuming and difficult to obtain tumor samples. METHODS: To address the above problems, we developed a noninvasive and convenient deep learning (DL) model based on Computed tomography (CT) imaging data for prediction of MET dysregulation. We introduced the unsupervised algorithm RK-net for automated image processing and utilized the MedSAM large model to achieve automated tissue segmentation. Based on the processed CT images, we developed a DL model (METnet). The model based on the grouped convolutional block. We evaluated the performance of the model over the internal test dataset using the area under the receiver operating characteristic curve (AUROC) and accuracy. We conducted subgroup analysis on the basis of clinical data of the lung cancer patients and compared the performance of the model in different subgroups. RESULTS: The model demonstrated a good discriminative ability over the internal test dataset. The accuracy of METnet was 0.746 with an AUC value of 0.793 (95% CI 0.714-0.871). The subgroup analysis revealed that the model exhibited similar performance across different subgroups. CONCLUSIONS: METnet realizes prediction of MET dysregulation in NSCLC, holding promise for guiding precise tumor diagnosis and treatment at the molecular level.

How neonatal diet affects the long-term development of rumination behavior, rumen fermentation and feed digestion in dairy calves fed a high milk level?

This study was to investigate growth performance, rumination development, rumen fermentation and feed digestion in young calves provided high volumes (about 20% of calf birth weight) of milk with or without forage inclusion and how these parameters correlate with each other. Immediately after birth, 160 newborn Holstein female calves (41.6 ± 4.2 kg of initial BW) were randomly divided into 2 treatments: 1) starter (CON, only starter) and 2) starter and hay (HAY, both starter and hay). The calves were fed their respective experimental diets from d 4 to 84, after which they were all introduced to similar diets until the end of the experiment on d 196. Treatment had no effect on growth and structural measurements throughout the experimental period. However, treatment had an effect on the other parameters, mainly during the post-weaning period. Forage supplementation tended to reduce starter dry matter intake (P = 0.05), while increasing the forage intake (P < 0.01) and the feed-to-gain ratio (P < 0.01). HAY calves had increased neutral detergent fiber (NDF) and physically effective NDF (peNDF) intakes (P < 0.05) and tended to lower (P < 0.01) starch intake compared to CON calves. The HAY calves had a higher rumination time (P < 0.01), ruminal pH (P < 0.01), and acetate-to-propionate ratio (P = 0.05) compared to the CON calves. Spearman correlation analysis showed that rumination time was positively related to the ruminal pH at d 84 (P = 0.01) and 196 (P = 0.02). The HAY calves had similar apparent total-tract digestibility of dry matter (DM), NDF and ether extract (EE), but lower digestibility of organic matter (OM, P = 0.03), crude protein (CP, P < 0.01) and starch (P < 0.01) compared to those of the CON calves at week 12. Furthermore, there were no positive relationships between rumination time and nutrient digestibility or between rumination time per kilogram DM and nutrient digestibility. In conclusion, feeding hay to calves fed a high milk level improved rumination during the post-weaning period only, without a concomitant effect on growth performance throughout the experimental period, suggesting no detrimental effect of feeding forage in calves fed high milk level.

Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals.

Postbiotics, which comprise inanimate microorganisms or their constituents, have recently gained significant attention for their potential health benefits. Extensive research on postbiotics has uncovered many beneficial effects on hosts, including antioxidant activity, immunomodulatory effects, gut microbiota modulation, and enhancement of epithelial barrier function. Although these features resemble those of probiotics, the stability and safety of postbiotics make them an appealing alternative. In this review, we provide a comprehensive summary of the latest research on postbiotics, emphasizing their positive impacts on both human and animal health. As our understanding of the influence of postbiotics on living organisms continues to grow, their application in clinical and nutritional settings, as well as animal husbandry, is expected to expand. Moreover, by substituting postbiotics for antibiotics, we can promote health and productivity while minimizing adverse effects. This alternative approach holds immense potential for improving health outcomes and revolutionizing the food and animal products industries.

Supplementation with Combined Additive Improved the Production of Dairy Cows and Their Offspring with Maintenance of Antioxidative Stability.

Oxidative stress damage in periparturient cows decreases both production and their health; supplementation with complex additives during the periparturient period has been used as an important strategy to enhance the antioxidant status and production of dairy cows. The periparturient cows not only risk a negative energy balance due to reduced dry matter intake but also represent a sensitive period for oxidative stress. Therefore, we have developed an immunomodulatory and nutritional regulation combined additive (INC) that hopefully can improve the immune status and production of cows during the periparturient period and their offspring health and growth by improving their antioxidant stress status. The INC comprised a diverse array of additives, including water-soluble and fat-soluble vitamins, Selenomethionine, and active dry Saccharomyces cerevisiae. Forty-five multiparous Holstein cows were randomly assigned to three treatments: CON (no INC supplementation, n = 15), INC30 (30 g/d INC supplementation, n = 15), and INC60 (60 g/d INC supplementation, n = 15) based on last lactation milk yield, body condition score, and parity. Newborn calves were administered 4 L of maternal colostrum originating from the corresponding treatment and categorized based on the treatment received by their respective dams. The INC not only served to maintain the antioxidative stress system of dairy cows during the periparturient period but also showed a tendency to improve the immune response (lower tumor necrosis factor and interleukin-6) during the perinatal period. A linear decrease in concentrations of alkaline phosphatase postpartum and ß-hydroxybutyrate was observed with INC supplementation. Milk fat yield, milk protein yield, and energy-corrected milk yield were also increased linearly with increasing additive supplementation. Calves in the INC30 group exhibited greater wither height and chest girth but no significant effect on average daily gain or body weight. The diarrhea frequency was linearly decreased with the incremental level of INC. Results indicate that supplementation with INC in peripartum dairy cows could be a major strategy to improve immune response, decrease inflammation, maintain antioxidant stress status in transition dairy cows, and have merit in their calves. In conclusion, this study underlines the benefits of INC supplementation during the transition period, as it improved anti-inflammatory capacity, could positively impact antioxidative stress capacity, and eventually enhanced the production performance of dairy cows and the health and growth of calves.

Initial diet shapes resistance-gene composition and fecal microbiome dynamics in young ruminants during nursing.

This study was conducted to examine how colostrum pasteurization affects resistance genes and microbial communities in calf feces. Forty female Holstein calves were randomly assigned to either the control (CON) group, which received unheated colostrum, or the pasteurized colostrum (PAT) group. The calves body weight was measured weekly before morning feeding. Calf starter intake were measured and recorded daily before morning feeding. Samples of colostrum were collected before feeding. Blood was collected on d 1 and 70 before morning feeding. Ten calves were randomly selected from each group (n = 20 calves total) for fecal sampling on d 3, 28, 56 and 70 for subsequent DNA extraction and metagenomic sequencing. Total bacterial counts in the colostrum were markedly higher in the CON group than in the PAT group. Pasteurized colostrum administration substantially reduced the ARO diversity and diminishes the abundance of Enterobacteriaceae, thereby decreasing their contribution to resistance genes. Pasteurization also reduced glucoside hydrolase-66 activity in 3-day-old calves which led to an increase in the activity of aminoglycoside antibiotics, resulting in 52.63 % of PAT-enriched bacteria acquiring aminoglycoside resistance genes. However, from the perspective of overall microbial community, the proportion of aminoglycoside, beta-lactam and tetracycline resistance genes carried by microbial community in PAT group was lower than CON group (P < 0.05). Fecal samples from the PAT group contained greater abundances of Subdoligranulum (P < 0.05) and Lachnospiraceae_NK4A136_group (P < 0.05) on days 28 and 70 compared to CON. Network analysis and abundance variations of the different bacteria obtained by linear discriminant analysis effect size analysis showed that pasteurized colostrum feeding reduced the interactions among related bacteria and maintained stability of the hind-gut microbiome. In conclusion, these findings underscore the intricate interactions between early diet, calf resistance-gene transmission and microbial dynamics, which should be carefully considered in calf-rearing practices.

ICTs and interventions in telerehabilitation and their effects on stroke recovery.

Telerehabilitation (TR) is a new model to provide rehabilitation services to stroke survivors. It is a promising approach to deliver mainstream interventions for movement, cognitive, speech and language, and other disorders. TR has two major components: information and communication technologies (ICTs) and stroke interventions. ICTs provide a platform on which interventions are delivered and subsequently result in stroke recovery. In this mini-review, we went over features of ICTs that facilitate TR, as well as stroke interventions that can be delivered via TR platforms. Then, we reviewed the effects of TR on various stroke disorders. In most studies, TR is a feasible and effective solution in delivering interventions to patients. It is not inferior to usual care and in-clinic therapy with matching dose and intensity. With new technologies, TR may result in better outcomes than usual care for some disorders. One the other hand, TR also have many limitations that could lead to worse outcomes than traditional rehabilitation. In the end, we discussed major concerns and possible solutions related to TR, and also discussed potential directions for TR development.

TRAF4 is crucial for the propagation of ST2+ memory Th2 cells in IL-33-mediated type 2 airway inflammation.

Tumor necrosis factor receptor (TNF)-associated factor 4 (TRAF4) is an important regulator of type 2 responses in the airway; however, the underlying cellular and molecular mechanisms remain elusive. Herein, we generated T cell-specific TRAF4-deficient (CD4cre-Traf4fl/fl) mice and investigated the role of TRAF4 in interleukin (IL)-33 receptor (ST2, suppression of tumorigenicity 2)-expressing memory Th2 cells (ST2+ mTh2) in IL-33-mediated type 2 airway inflammation. We found that in vitro polarized TRAF4-deficient (CD4cre- Traf4fl/fl) ST2+ mTh2 cells exhibited decreased IL-33-induced proliferation as compared with TRAF4-sufficient (Traf4fl/fl) cells. Moreover, CD4cre-Traf4fl/fl mice showed less ST2+ mTh2 cell proliferation and eosinophilic infiltration in the lungs than Traf4fl/fl mice in the preclinical models of IL-33-mediated type 2 airway inflammation. Mechanistically, we discovered that TRAF4 was required for the activation of AKT/mTOR and ERK1/2 signaling pathways as well as the expression of transcription factor Myc and nutrient transporters (Slc2a1, Slc7a1, and Slc7a5), signature genes involved in T cell growth and proliferation, in ST2+ mTh2 cells stimulated by IL-33. Taken together, the current study reveals a previously unappreciated role of TRAF4 in ST2+ mTh2 cells in IL-33-mediated type 2 pulmonary inflammation, opening up avenues for the development of new therapeutic strategies.

TRAF4 is crucial for ST2+ memory Th2 cell expansion in IL-33-driven airway inflammation.

Tumor necrosis factor receptor-associated factor 4 (TRAF4) is an important regulator of type 2 responses in the airway; however, the underlying cellular and molecular mechanisms remain elusive. Herein, we generated T cell-specific TRAF4-deficient (CD4-cre Traf4fl/fl) mice and investigated the role of TRAF4 in memory Th2 cells expressing IL-33 receptor (ST2, suppression of tumorigenicity 2) (ST2+ mTh2 cells) in IL-33-mediated type 2 airway inflammation. We found that in vitro-polarized TRAF4-deficient (CD4-cre Traf4fl/fl) ST2+ mTh2 cells exhibited decreased IL-33-induced proliferation as compared with TRAF4-sufficient (Traf4fl/fl) cells. Moreover, CD4-cre Traf4fl/fl mice showed less ST2+ mTh2 cell proliferation and eosinophilic infiltration in the lungs than Traf4fl/fl mice in the preclinical models of IL-33-mediated type 2 airway inflammation. Mechanistically, we discovered that TRAF4 was required for the activation of AKT/mTOR and ERK1/2 signaling pathways as well as the expression of transcription factor Myc and nutrient transporters (Slc2a1, Slc7a1, and Slc7a5), signature genes involved in T cell growth and proliferation, in ST2+ mTh2 cells stimulated by IL-33. Taken together, the current study reveals a role of TRAF4 in ST2+ mTh2 cells in IL-33-mediated type 2 pulmonary inflammation, opening up avenues for the development of new therapeutic strategies.

Application of Near-Infrared Reflectance Spectroscopy for Predicting Chemical Composition of Feces in Holstein Dairy Cows and Calves.

Traditional methods for determining the chemical composition of cattle feces are uneconomical. In contrast, near-infrared reflectance spectroscopy (NIRS) has emerged as a successful technique for assessing chemical compositions. Therefore, in this study, the feasibility of NIRS in terms of predicting fecal chemical composition was explored. Cattle fecal samples were subjected to chemical analysis using conventional wet chemistry techniques and a NIRS spectrometer. The resulting fecal spectra were used to construct predictive equations to estimate the chemical composition of the feces in both cows and calves. The coefficients of determination for calibration (RSQ) were employed to evaluate the calibration of the predictive equations. Calibration results for cows (dry matter [DM], RSQ = 0.98; crude protein [CP], RSQ = 0.93; ether extract [EE], RSQ = 0.91; neutral detergent fiber [NDF], RSQ = 0.82; acid detergent fiber [ADF], RSQ = 0.89; ash, RSQ = 0.84) and calves (DM, RSQ = 0.92; CP, RSQ = 0.89; EE, RSQ = 0.77; NDF, RSQ = 0.76; ADF, RSQ = 0.92; ash, RSQ = 0.97) demonstrated that NIRS is a cost-effective and efficient alternative for assessing the chemical composition of dairy cattle feces. This provides a new method for rapidly predicting fecal chemical content in cows and calves.

The age at first consumption of forage in calves and its effect on growth and rumination in the short- and long-term.

BACKGROUND: Previous investigations into the effect of dietary forage on calf performance have been inconsistent, and there is a paucity of information exploring the effect of age on the growth performance and rumination of calves. Eighty-four female Holstein calves (41.5 ± 4.2 kg) were enrolled at birth, a subset of the calves were fed calf starter only (CON, n = 21) while the rest (n = 63) were classified into three treatment groups: the early (EHAY, n = 26, 5.1 ± 0.8 d), the middle (MHAY, n = 21, 7.9 ± 0.8 d) and the late (LHAY, n = 16, 12.1 ± 1.4 d) hay consumers. The short-term effect of the age at first forage consumption (AFF) on calves' feed intake was monitored until d 84. In addition, the long-term effects of AFF on body weight, structural growth and rumination behavior were recorded until d 196. Rumen samples were collected on d 1, 7, 35, 84 and 196 to analyze the rumen fermentation, while fecal samples were collected from d 78 to 84 to estimate digestibility parameters. RESULTS: Treatment had no effect on feed intake. While, the EHAY calves tended to have lower BW and ADG compared to LHAY and CON calves. Several total-tract apparent digestibility parameters and digestible nutrients intake were significantly lower in EHAY calves compared with CON and LHAY calves. Calves in the EHAY group tended to begin ruminating ealier, while CON calves were the latest (12.3 vs. 15.5 days of age). A treatment and time interaction was present for rumination time due to greater rumination in calves consuming hay compared to CON calves in week 10 to 12, the differences in rumination disappeared afterwards, no long-lasting significant differences in the rumination and rumen fermentation parameters were found between treatments. CONCLUSIONS: In conclusion, this study showed that hay consumption earlier in life (in the first week, around 5 days of life) could negatively affect the growth of the calf in the short and long term. Compared to consuming hay from the second week (around 12 days of life) or feeding concentrate only without hay, starting to consume hay from the first week could compromise nutrient digestibility and digestible nutrient intake independent of developing rumination behaviour and rumen fermentation.

Glucose Regulates Glucose Transport and Metabolism via mTOR Signaling Pathway in Bovine Placental Trophoblast Cells.

It has been confirmed that improving the energy level of the diet contributed to the greater reproductive performance and birth weight of calves in periparturient dairy cows. To investigate the effect of glucose on nutrient transport during fetal development, the bovine placental trophoblast cells (BPTCs) were cultured in media with different glucose concentrations (1, 2, 4, 8, or 16 mg/mL). Subsequently, the BPTCs were cultured in media with 1, 8 mg/mL glucose and 8 mg/mL glucose plus 100 nmol/L rapamycin (the inhibitor of mTOR pathway). Compared with the 1 mg/mL glucose, the addition of 8 mg/mL glucose stimulated cell proliferation, upregulated the mRNA abundance of the glucose transporter GLUT1 and GLUT4, and increased the activity of glucose metabolism-related enzyme glucose-6-phosphate dehydrogenease (G6PD), lactate dehydrogenase (LDHA) and phosphoglycerate kinase 1 (PGK1), as well as adenosine-triphosphate (ATP) content (p < 0.05).Furthermore, compared with the treatment of 1 mg/mL glucose, adding 8 mg/mL of glucose-upregulated gene expression in the mTOR signaling pathway, including phosphatidylinositol3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase 2 (P70S6K) (p < 0.05).The supplementation of rapamycin downregulated the gene and protein expression of the mTOR signaling pathway, including mTOR, P70S6K, EIF4E-binding protein 1 (4EBP1), hypoxia-inducible factor 1-alpha (HIF-1α) and gene expression of glucose transporter upregulated by 8 mg/mL glucose (p < 0.05). Thus, these results indicated that the addition of 8 mg/mL glucose regulated the glucose transport and metabolism in BPTCs through the mTOR signaling pathway, thereby promoting the supply of nutrients to fetus.

RNA-Binding Protein HuR Promotes Airway Inflammation in a House Dust Mite-Induced Allergic Asthma Model.

Mounting evidence indicates that interleukin 17 (IL-17) is critically involved in the pathogenesis of severe asthma. We have previously reported that upon IL-17 stimulation, Act1, an IL-17-receptor-complex adaptor, directly binds to its target mRNAs and utilizes other proteins, such as HuR, to upregulate mRNA stability and translation. HuR mRNA targets include multiple asthma-related genes. In this study, we have used house dust mite (HDM), a natural allergen, to test the role of HuR in the pathogenesis of allergic asthma. We found that HuR deletion in airway epithelium diminished HDM-induced lung inflammation, including neutrophil and eosinophil infiltration. While Th2 cytokines were not altered, the production of CXCL1, CXCL5 and CCL11 chemokines was significantly diminished. Airway smooth muscle (ASM) cells contribute to the pathogenesis of allergic asthma by orchestrating inflammatory and remodeling responses. We found that IL-17 treatment of ASM cells induced translocation of HuR from nucleus to cytoplasm, where it bound directly to Cxcl1 and Ccl11 mRNA. Deletion of HuR in ASM cells decreased their proliferation as well as CXCL1 and CCL11 production in response to IL-17. Taken together, our findings demonstrate the importance of HuR-mediated regulation of gene expression to the pathogenesis of allergic asthma, in both airway epithelial and ASM cells.

A Combination of Novel Microecological Agents and Molasses Role in Digestibility and Fermentation of Rice Straw by Facilitating the Ruminal Microbial Colonization.

In this study, we evaluated the effect of microecological agents (MA) combined with molasses (M) on the biodegradation of rice straw in the rumen. Rice straw was pretreated in laboratory polyethylene 25 × 35 cm sterile bags with no additive control (Con), MA, and MA + M for 7, 15, 30, and 45 days, and then the efficacy of MA + M pretreatment was evaluated both in vitro and in vivo. The scanning electron microscopy, X-ray diffraction analysis, and Fourier-transform infrared spectroscopy results showed that the MA or MA + M pretreatment altered the physical and chemical structure of rice straw. Meanwhile, the ruminal microbial attachment on the surface of rice straw was significantly increased after MA+M pretreatment. Furthermore, MA + M not only promoted rice straw fermentation in vitro but also improved digestibility by specifically inducing rumen colonization of Prevotellaceae_UCG-001, Butyrivibrio, and Succinimonas. Altogether, we concluded that microecological agents and molasses could be the best choices as a biological pretreatment for rice straw to enhance its nutritive value as a ruminant's feed.

Gut microbiota-derived ursodeoxycholic acid from neonatal dairy calves improves intestinal homeostasis and colitis to attenuate extended-spectrum ß-lactamase-producing enteroaggregative Escherichia coli infection.

BACKGROUND: Antimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum ß-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear. RESULTS: We investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production. CONCLUSIONS: This study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.