Rumen bacterial cluster identification and its influence on rumen metabolites and growth performance of young goats.

Enterotypes, which are defined as bacterial clusters in the gut microbiome, have been found to have a close relationship to host metabolism and health. However, this concept has never been used in the rumen, and little is known about the complex biological relationships between ruminants and their rumen bacterial clusters. In this study, we used young goats (n = 99) as a model, fed them the same diet, and analyzed their rumen microbiome and corresponding bacterial clusters. The relationships between the bacterial clusters and rumen fermentation and growth performance in the goats were further investigated. Two bacterial clusters were identified in all goats: the P-cluster (dominated by genus Prevotella, n = 38) and R-cluster (dominated by Ruminococcus, n = 61). Compared with P-cluster goats, R-cluster goats had greater growth rates, concentrations of propionate, butyrate, and 18 free amino acids¸ and proportion of unsaturated fatty acids, but lower acetate molar percentage, acetate to propionate ratio, and several odd and branched chain and saturated fatty acids in rumen fluid (P < 0.05). Several members of Firmicutes, including Ruminococcus, Oscillospiraceae NK4A214 group, and Christensenellaceae R-7 group were significantly higher in the R-cluster, whereas Prevotellaceae members, such as Prevotella and Prevotellaceae UCG-003, were significantly higher in P-cluster (P < 0.01). Co-occurrence networks showed that R-cluster enriched bacteria had significant negative correlations with P-cluster enriched bacteria (P < 0.05). Moreover, we found the concentrations of propionate, butyrate and free amino acids, and the proportions of unsaturated fatty acids were positively correlated with R-cluster enriched bacteria (P < 0.05). The concentrations of acetate, acetate to propionate ratio, and the proportion of odd and branched chain and saturated fatty acids were positively correlated with P-cluster enriched bacteria (P < 0.05). Overall, our results indicated that rumen bacterial clusters can influence rumen fermentation and growth performance of young goats, which may shed light on modulating the rumen microbiome in early life to improve the growth performance of ruminant animals.

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

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

[Recent application advances of covalent organic frameworks for solid-phase extraction].

Covalent organic frameworks (COFs) are a type of crystalline porous polymers. It firstly prepared by thermodynamically controlled reversible polymerization to obtain chain units and connecting small organic molecular building units with a certain symmetry. These polymers are widely used in gas adsorption, catalysis, sensing, drug delivery, and many other fields. Solid-phase extraction (SPE) is a fast and simple sample pretreatment technology that can enrich analytes and improve the accuracy and sensitivity of analysis and detection; it is extensively employed in food safety detection, environmental pollutant analysis, and several other fields. How to improve the sensitivity, selectivity, and detection limit of the method during sample pretreatment have become a topic of great interest. COFs have recently been applied to sample pretreatment owing to their low skeleton density, large specific surface area, high porosity, good stability, facile design and modification, simple synthesis, and high selectivity. At present, COFs have also attracted extensive attention as new extraction materials in the field of SPE. These materials have been applied to the extraction and enrichment of diverse types of pollutants in food, environmental, and biological samples, such as heavy metal ions, polycyclic aromatic hydrocarbons, phenol, chlorophenol, chlorobenzene, polybrominated diphenyl ethers, estrogen, drug residues, pesticide residues, etc. COFs can be synthesized from different materials and exert different effects on different extracts. New types of COFs can also be synthesized via modification to achieve better extraction effects. In this work, the main types and synthesis methods of COFs are introduced, and the most important applications of COFs in the fields of food, environment and biology in recent years are highlighted. The development prospects of COFs in the field of SPE are also discussed.

Potential roles of the rectum keystone microbiota in modulating the microbial community and growth performance in goat model.

BACKGROUND: Ruminal microbiota in early life plays critical roles in the life-time health and productivity of ruminant animals. However, understanding of the relationship between gut microbiota and ruminant phenotypes is very limited. Here, the relationship between the rectum microbiota, their primary metabolites, and growth rate of a total of 76 young dairy goats (6-month-old) were analyzed, and then 10 goats with the highest or lowest growth rates respectively were further compared for the differences in the rectum microbiota, metabolites, and animal's immune parameters, to investigate the potential mechanisms by which the rectum microbiota contributes to the health and growth rate. RESULTS: The analysis of Spearman correlation and microbial co-occurrence network indicated that some keystone rectum microbiota, including unclassified Prevotellaceae, Faecalibacterium and Succinivibrio, were the key modulators to shape the rectum microbiota and closely correlated with the rectum SCFA production and serum IgG, which contribute to the health and growth rate of young goats. In addition, random forest machine learning analysis suggested that six bacterial taxa in feces could be used as potential biomarkers for differentiating high or low growth rate goats, with 98.3% accuracy of prediction. Moreover, the rectum microbiota played more important roles in gut fermentation in early life (6-month-old) than in adulthood stage (19-month-old) of goats. CONCLUSION: We concluded that the rectum microbiota was associated with the health and growth rate of young goats, and can be a focus on the design of the early-life gut microbial intervention.

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

Introduction: Multiple litters are accompanied by low birth weight, low survival rates, and growth rates in goats during early life. Regulating rumen microbiota structure can indirectly or directly affect host metabolism and animal growth. However, the relationship between high litter size and rumen microbiome, rumen fermentation, and growth performance in goat kids is unclear. Methods: In the present study, thirty 6-month-old, female goats were investigated, of which 10 goats were randomly chosen from single, twin and triplet goats respectively, and their birth weight was recorded. From birth, all goats were subjected to the same feed and management practices. Individual weaning and youth body weight were measured, and the rumen fluid samples were collected to characterize the bacterial communities and to determine the ruminal volatile fatty acids (VFA), free amino acids (AA), and free fatty acids (FA) concentration of those young goats. Results and Discussion: Compared with the single and twin goats, triplet goats have lower weaning and youth body weight and average daily gain (ADG). Ruminal propionate, butyrate, and total VFA were decreased in triplet goats. Meanwhile, ruminal AA, such as branched chain amino acids (BCAA), essential amino acids (EAA), unsaturated fatty acids (UFA), and monounsaturated fatty acids (MUFA) were decreased, while saturated fatty acids (SFA) and odd and branched chain fatty acids (OBCFA) were increased in triplet goats. Our results also revealed that litter size significantly affected the rumen bacterial communities, and triplet goats had a lower the Firmicutes: Bacteroidota ratio, the abundance of Firmicutes phylum, Rikenellaceae family, and Rikenellaceae RC9 gut group, and had a higher proportion of Prevotellaceae family, and several genera of Prevotellaceae, such as Prevotella, and unclassified f Prevotellaceae. Furthermore, Spearman's correlation network analysis showed that the changes in the rumen bacteria were associated with changes in rumen metabolites. In conclusion, this study revealed that high litter size could bring disturbances to the microbial communities and decrease the rumen fermentation efficiency and growth performance, which can be utilized to better understand variation in microbial ecology that will improve growth performance in triplet goats.

Microbial Enterotypes Shape the Divergence in Gut Fermentation, Host Metabolism, and Growth Rate of Young Goats.

Enterotypes can be useful tools for studying the gut microbial community landscape, which is thought to play a crucial role in animal performance. However, few studies have been carried out to identify enterotypes and their associations with growth performance in young goats. In this study, two enterotypes were categorized in 76 goats: cluster 1 (n = 39) and cluster 2 (n = 37). Compared to cluster 2, cluster 1 had greater growth rates, the concentrations of acetate, propionate, valerate, and total volatile fatty acids (VFA) in the gut. Several serum glycolipid metabolism parameters, including glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were also increased in cluster 1, while serum IgG was decreased in cluster 1. Using α-diversity analysis, we found a microbiome with lower richness and diversity in cluster 1. Some gut bacteria, including Succinivibrio and several members of the Prevotellaceae family, were enriched in cluster 1, while Christensenellaceae R-7 group, Romboutsia, and Clostridium sensu stricto 1 were enriched in cluster 2. A co-occurrence network analysis revealed that the differential interaction patterns existed in two enterotypes, and microbial function prediction suggested that some nutrient metabolism-related pathways, including amino acid biosynthesis and starch and sucrose metabolism, were enriched in cluster 1. Furthermore, a correlation analysis showed that enterotype-related bacteria were closely correlated with gut fermentation, serum biochemistry, and growth rate. Overall, our data provide a new perspective for understanding enterotype characteristics in goats, offering insights into important microbial interaction mechanisms for improving the growth performance of ruminant animals. IMPORTANCE The intricate relationships between a host animal and its resident gut microbiomes provide opportunities for dealing with energy efficiency and production challenges in the livestock industry. Here, we applied the enterotype concept to the gut microbiome in young goats and found that it can be classified into two enterotypes which are apparently associated with divergences in gut fermentation, blood biochemistry, and goat growth rates. The microbial co-occurrence networks and function predictions differed between the two enterotypes, suggesting that the formation of host phenotype may be modified by different bacterial features and complex bacterial interactions. The characteristics of enterotypes related to growth performance in young goats may enable us to improve long-term production performance in goat industry by modulating the gut microbiome during early life.

Making Appropriate New Choices Through Unconscious Thought Based on New Goals.

This research examines whether appropriate choices can be made based on a new goal through unconscious thought. The experimental materials are four mobile phones, one suitable for older adults and the other for younger people. The results of Experiment 1 show that when the goal was changed from judging whether a mobile phone is suitable for older adults to judging whether it is suitable for younger people, the scores of the participants in the unconscious thought group-that mobile phones are objectively suitable for older adults-were significantly higher than those for the group which thought that mobile phones are objectively suitable for young people. In Experiment 2, the immediate decision-making group was added, which ruled out the possibility that the participants had already made a choice during the information presentation process. The results of this study show that unconscious thought can make appropriate new choices based on new goals.

Stat5-/- CD4+ T cells elicit anti-melanoma effect by CD4+ T cell remolding and Notch1 activation.

Signal transducers and activators of transcription 5 (Stat5) is known to engage in regulating the differentiation and effector function of various subsets of T helper cells. However, how Stat5 regulates the antitumor activity of tumor-infiltrating CD4+ T cells is largely unknown. Here, we showed that mice with specific deletion of Stat5 in CD4+ T cells were less susceptible to developing subcutaneous and lung metastatic B16 melanoma with CD4+ tumor-infiltrating lymphocytes (TILs) remolding. Especially, we confirmed that Stat5-deficient CD4+ naïve T cells were prone to polarization of two subtypes of Th17 cells: IFN-γ+ and IFN-γ- Th17 cells, which exhibited increased anti-melanoma activity through enhanced activation of Notch1 pathway compared with wild type Th17 cells. Our study therefore revealed a novel function of Stat5 in regulating tumor-specific Th17 cell differentiation and function in melanoma. This study also provided a new possibility for targeting Stat5 and other Th17-associated pathways to develop novel immunotherapies for melanoma patients.

Preoperative Ultra-Short-Course Chemotherapy Combined with Surgery for the Treatment of Chest Wall Tuberculosis.

OBJECTIVE: To investigate the safety and efficacy of preoperative ultra-short-course chemotherapy, combined with surgical treatment for chest wall tuberculosis and summarize our experience in this regard, to provide a reference for national and international clinicians. METHODS: A retrospective analysis was conducted of the clinical data, preoperative anti-tuberculosis duration, and postoperative recurrence rate in 263 patients with chest wall tuberculosis spanning 5 years. RESULTS: Overall, 263 patients were treated with anti-tuberculosis drugs for about ± 12.49 days during the preoperative period. Simple chest wall tuberculosis was treated for ± 5.87 days and composite chest wall tuberculosis for ± 5.11 days. The postoperative recurrence rate of chest wall tuberculosis was 3.80%, which was close to or lower than the recurrence rate of routine preoperative anti-tuberculous therapy in patients subjected to ultra-short-range anti-tuberculosis treatment before surgery. CONCLUSION: Preoperative ultra-short-course chemotherapy combined with surgical treatment of chest wall tuberculosis did not increase the recurrence rate of chest wall tuberculosis; moreover, it could effectively shorten hospitalization time and improve patient compliance. Full-line anti-tuberculosis treatment and complete resolution of tuberculosis infections are crucial to curing chest wall tuberculosis.

Analysing the Clinical Features of Pneumomediastinum Associated with Diabetic Ketoacidosis in 79 Cases.

OBJECTIVE: To analyse the clinical features of pneumomediastinum associated with DKA (diabetic ketoacidosis) to improve clinicians' understanding of the disease. METHODS: A total of 78 patients with pneumomediastinum associated with DKA were identified in the literature search, and one patient treated in our hospital was included. The clinical features of the 79 patients were retrospectively analysed, and the pathogenesis, clinical symptoms, diagnostic methods, treatment strategies and prognoses were explored. RESULTS: All cases were confirmed by chest CT (computed tomography), and Kussmaul respiration, severe vomiting, chest pain were common symptoms. The main treatment principle was to correct acidosis and treat the primary disease. The majority of patients recovered within 1-2 weeks, and only 2 patients died. CONCLUSION: Pneumomediastinum associated with DKA is a rare disease, and it has a benign course when an early diagnosis is made and aetiological treatment is administered.

Development of selective mono or dual PROTAC degrader probe of CDK isoforms.

Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation. In discovering inhibitors of these CDKs, toxicity associated with off-target effect on other CDK homologs often posts as a clinical issue and hinders their further therapeutic development. To improve efficacy and reduce toxicity, here, using the Proteolysis Targeted Chimeras (PROTACs) approach, we design and further optimize small molecule degraders targeting multiple CDKs. We showed that heterobifunctional compound A9 selectively degraded CDK2. We also identified a dual-degrader, compound F3, which potently induced degradation of both CDK2 (DC50: 62 nM) and CDK9 (DC50: 33 nM). In human prostate cancer PC-3 cells, compound F3 potently inhibits cell proliferation by effectively blocking the cell cycle in S and G2/M phases. Our preliminary data suggests that PROTAC-oriented CDK2/9 degradation is potentially an effective therapeutic approach.

A Hydrostatic Bearing Test System for Measuring Bearing Load Using Magnetic-Fluid Lubricants.

This paper conducts a study on the design of a hydrostatic bearing test system. It involves the determination of viscous properties of magnetic-fluid lubricants. The load of a hydrostatic thrust bearing using a water-based magnetite nanofluid of varying volume flow rate is measured under an applied external induction field via the test system. Results reveal that the presence of nanoparticles in a carrier liquid would cause an enhanced bearing load. Such an effect could be further magnified by increasing the lubricant volume flow rate or the external induction field strength.

Monte Carlo simulation of linac irradiation with dynamic wedges.

This study aims to simulate the dose distributions of LINAC with dynamic wedges (DWs) under various field sizes and wedge angles by the BEAMnrc code with DYNJAWS component module. These were compared with those calculated by the treatment planning system (TPS) and the measured data. All percentage depth doses (PDDs) were found to be in good agreement between TPS, Monte Carlo (MC) and measurements made in open fields and fields with DWs. For dose profiles, compared with the MC and the measurements, TPS gives reliable results for large field sizes (>10 × 10 cm(2)) but results in significant errors in small field sizes (5 × 5 cm(2)). The entrance surface doses calculated by TPS were found to be significantly overestimated. For depths deeper than 0.5 cm, TPS yields PDDs in agreement with MC simulations.