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Homeodomain-only protein homeobox (HOPX) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (HDAC), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). HDACs play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether HOPX affects AML progression by interacting with HDAC2 protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker HOPX. The interaction network of HOPX was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between HOPX and HDAC2 was observed using endogenous and exogenous immunoprecipitation. HOPX is highly expressed in AML cells. Further research uncovered that low expression of HOPX can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, HOPX induced AML differentiation blockage and malignant progression through interaction with HDAC. HOPX can serve as a prognostic marker for AML and can interact with HDAC2 to induce AML differentiation blockage and malignant progression.

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The intricate and protracted process of dentin formation has been extensively explored, thanks to the significant advancements facilitated by the use of animal models and related techniques. Despite variations in their effectiveness, taking into account factors such as sensitivity, visibility, and reliability, these models or techniques are indispensable tools for investigating the complexities of dentin formation. This article focuses on the latest advances in animal models and related technologies, shedding light on the key molecular mechanisms that are essential in dentin formation. A deeper understanding of this phenomenon enables the careful selection of appropriate animal models, considering their suitability in unraveling the underlying molecular intricacies. These insights are crucial for the advancement of clinical drugs targeting dentin-related ailments and the development of comprehensive treatment strategies throughout the duration of the disease.

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Protein grass hay (PGH) was used as a new feed source for lambs to study its effect on fattening performance and meat quality. Fifty-six male lambs were allotted to four experimental groups and fed for eight weeks either alfalfa hay (AH)-based diet (control) or diets in which AH was replaced with 33 %, 66 %, or 99 % PGH. The inclusion of PGH did not affect final body weight, dry matter intake, average daily gain, feed conversion ratio, or carcass weight. Moreover, substituting AH with PGH at any level did not influence the ruminal fermentation or serum biochemical parameters, meat color, water holding capacity, shear force, or amino acid profile. However, relative liver weight was increased with 66 % substitutions. Furthermore, replacing 99 % AH with PGH decreased the meat's pH at 24 h. Higher levels of C18:3n-3, C20:5n-3, and total n-3 PUFA and a lower ratio of n-6: n-3 PUFA were also observed in meat from lambs fed PGH at 99 %. These findings suggest that PGH could be incorporated into the lamb's diet up to 99 % without compromising fattening performance and body health while improving their meat n-3 PUFA deposition.

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The rumen microbiome plays an important role in providing energy and protein to the host. Manipulation of rumen microbiome during early life may have a long-term beneficial effect on the health, growth performance, and feed efficiency of ruminants. To better understand the profiles and functional potentials of rumen microbiome in young ruminants, metagenomic binning was performed to investigate the rumen microbiome of goat kids from one to 84 days of age. A total of 797 metagenome-assembled genomes (MAGs) were recovered from the rumen of 42 Laiwu black goat kids. Our findings provide fundamental knowledge of the rumen microbiome during early life based on metagenomic binning, which may provide insights into effective strategies to achieve long-term beneficial effects on animal health and production.

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Motivated by the driving force to address global water scarcity, industrial water resources, as the second largest consumption of water resources, its security assessment plays a crucial role in improving the current situation. Hence, this paper proposes a novel methodology to conduct the industrial water resources security (IWRS) assessment. Firstly, a more targeted assessment system based on the framework of the Pressure-State-Response (P-S-R) on IWRS is established. Then, enhanced with a double hierarchy hesitant fuzzy linguistic term set (DHHFLTS), the Best-Worst Method (BWM) now determines subjective weights through DHHFLTS-BWM (DF-BWM). By introducing the Criteria Importance Through Intercriteria Correlation (CRITIC) method, which considers the indicator interactions, objective weights are obtained to modify the subjective weights. Furthermore, the global dominance of all alternatives is calculated by a TODIMSort method and grading them. Moreover, 16 cities in Anhui Province are taken as examples to assess IWRS in the decade from 2011 to 2020. Comparative analysis with original BWM, time series analysis, sensitivity analysis on loss attenuation coefficient, coupling and coordination analysis and obstacle analysis on all indicators are conducted to verify the rationality, effectiveness, and stability of the proposed assessment methodology. Simultaneously, explore the existing issues within IWRS. It can be seen from the results that the performance of Lu'an and Huainan cities is relatively better, while Ma'anshan city shows relatively poorer performance. In addition, per capita water resources and wastewater treatment facilities have a significant impact on the IWRS. Finally, some management suggestions are proposed to enhance the scientific and effective management of industrial water resources and ensure their sustainable utilization.

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BACKGROUND: The average daily gain (ADG) of preweaning calves significantly influences their adult productivity and reproductive performance. Gastrointestinal microbes are known to exert an impact on host phenotypes, including ADG. The aim of this study was to investigate the mechanisms by which gastrointestinal microbiome regulate ADG in preweaning calves and to further validate them by isolating ADG-associated rumen microbes in vitro. RESULTS: Sixteen Holstein heifer calves were selected from a cohort with 106 calves and divided into higher ADG (HADG; n = 8) and lower ADG (LADG; n = 8) groups. On the day of weaning, samples of rumen contents, hindgut contents, and plasma were collected for rumen metagenomics, rumen metabolomics, hindgut metagenomics, hindgut metabolomics, and plasma metabolomics analyses. Subsequently, rumen contents of preweaning Holstein heifer calves from the same dairy farm were collected to isolate ADG-associated rumen microbes. The results showed that the rumen microbes, including Pyramidobacter sp. C12-8, Pyramidobacter sp. CG50-2, Pyramidobacter porci, unclassified_g_Pyramidobacter, Pyramidobacter piscolens, and Acidaminococcus fermentans, were enriched in the rumen of HADG calves (LDA > 2, P < 0.05). Enrichment of these microbes in HADG calves' rumen promoted carbohydrate degradation and volatile fatty acid production, increasing proportion of butyrate in the rumen and ultimately contributing to higher preweaning ADG in calves (P < 0.05). The presence of active carbohydrate degradation in the rumen was further suggested by the negative correlation of the rumen microbes P. piscolens, P. sp. C12-8 and unclassified_g_Pyramidobacter with the rumen metabolites D-fructose (R < - 0.50, P < 0.05). Widespread positive correlations were observed between rumen microbes (such as P. piscolens, P. porci, and A. fermentans) and beneficial plasma metabolites (such as 1-pyrroline-5-carboxylic acid and 4-fluoro-L-phenylalanine), which were subsequently positively associated with the growth rate of HADG calves (R > 0.50, P < 0.05). We succeeded in isolating a strain of A. fermentans from the rumen contents of preweaning calves and named it Acidaminococcus fermentans P41. The in vitro cultivation revealed its capability to produce butyrate. In vitro fermentation experiments demonstrated that the addition of A. fermentans P41 significantly increased the proportion of butyrate in the rumen fluid (P < 0.05). These results further validated our findings. The relative abundance of Bifidobacterium pseudolongum in the hindgut of HADG calves was negatively correlated with hindgut 4-hydroxyglucobrassicin levels, which were positively correlated with plasma 4-hydroxyglucobrassicin levels, and plasma 4-hydroxyglucobrassicin levels were positively correlated with ADG (P < 0.05). CONCLUSIONS: This study's findings unveil that rumen and hindgut microbes play distinctive roles in regulating the preweaning ADG of Holstein heifer calves. Additionally, the successful isolation of A. fermentans P41 not only validated our findings but also provided a valuable strain resource for modulating rumen microbes in preweaning calves. Video Abstract.

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BACKGROUND: It has been proven that immune disorders are one of the vital risk factors of recurrent pregnancy loss (RPL), and the presence of food intolerance seems to play an essential role in this. However, the impact of immune status induced by food intolerance on RPL has not been reported. This study utilized a targeted diet avoiding food intolerance as much as possible for each participant to investigate their effects on pregnancy outcomes in RPL patients with positive autoimmune markers. METHODS: From January 2020 to May 2021, fifty-eight patients with RPL were enrolled. They were divided into two groups based on the presence of autoantibodies: the autoantibody-positive group (AP, n = 29) and the autoantibody-negative group (AN, n = 29). Their food-specific immunoglobulin (Ig) G antibodies for 90 foods were tested using enzyme-linked immunosorbent assay (ELISA). The levels of immune parameters and the presence of gastrointestinal discomforts (diarrhea or constipation, eczema, and mouth ulcers) were recorded before and after dietary conditioning, followed by the analysis of pregnancy outcomes. RESULTS: Compared to the AN group, the patients in the AP group showed immune disorders at baseline, such as reduced levels of IL-4 and complement C3, and increased levels of IL-2 and total B cells. These parameters within the AP group were significantly improved after dietary conditioning that avoided food intolerance, while no significant changes were observed in the AN group. Patients in the AP group had significantly higher food-specific IgG antibodies for cow's milk (89.66% vs. 48.28%, p < .001), yolk (86.21% vs. 27.59%, p < .001), bamboo shoots (86.21% vs. 44.83%, p < .001) compared to those in the AN group. Additionally, gastrointestinal discomforts including diarrhea or constipation, eczema, and mouth ulcers were more common in the AP group than in the AN group. After 3-month dietary conditioning, these significantly improved characteristics were only observed in the AP group (p < .001). Finally, the baby-holding rate was higher in the AP group compared to the AN group (p < .05). CONCLUSIONS: The RPL patients in the AN group did not exhibit immune disorders, whereas those in the AP group experienced immune disorders and gastrointestinal discomforts. For patient with positive autoantibodies, dietary intervention may mitigate immune disorders and gastrointestinal discomforts, presenting a promising approach to enhance pregnancy outcomes.

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A novel, to the best of our knowledge, photodetector with a metalens packaging module used as the visible light communication (VLC) receiver is proposed and designed. An LED consisting of red, green, blue, and yellow chips (RGBY-LED) is adopted as the transmitter for intensity modulation direct detection VLC systems. A metalens array with a numerical aperture (NA) of 0.707 used as a polarization-insensitive planar lens of the VLC system receiver is designed at wavelengths of 457, 523, 592, and 623 nm corresponding to blue, green, yellow, and red for high efficiency. Compared with a traditional Fresnel lens positive-intrinsic-negative (PIN) photodetector module as the VLC receiver, the introduction of a metalens module can decrease the form factor of the VLC receiver module and, in particular, it is much thinner. The combination of the multi-color LED transmitter and photodetector metalens packaging module receiver can increase the modulation bandwidth due to four different wavelengths used for the VLC system. Finite-difference time domain (FDTD) simulations are performed to validate the performance of the photodetector with a metalens module. It is revealed that the corresponding efficiencies of 57.5%, 55.4%, 57%, and 56.3% were achieved at wavelengths of 623, 592, 523, and 457 nm, respectively, based on a metalens array with a 0.707 NA and 2.5 µm radius of the active area of the photodetector. It is a promising technology for indoor VLC systems such as those for smart phones and other Internet of Things devices due to the need for compact packaging for the receiver.

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Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (p = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

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Inhibition of methyl-coenzyme M reductase can suppress the activity of ruminal methanogens, thereby reducing enteric methane emissions of ruminants. However, developing specific and environmentally friendly inhibitors is a challenging endeavor. To identify a natural and effective methane inhibitor that specifically targets methyl-coenzyme M reductase, molecular docking technology was employed to screen a library of phytogenic compounds. A total of 52 candidate compounds were obtained through molecular docking technique. Rosmarinic acid (RA) was one of the compounds that could traverse a narrow channel and bind to the active sites of methyl-coenzyme M reductase, with a calculated binding free energy of -9.355 kcal/mol. Furthermore, the effects of rosmarinic acid supplementation on methane production, rumen fermentation, and the microorganism's community in dairy cows were investigated through in vitro rumen fermentation simulations according to a random design. Supplementation of RA resulted in a 15% decrease in methane production compared with the control. In addition, RA increased the molar proportion of acetate and propionate, whereas the sum of acetate and butyrate divided by propionate was decreased. At the bacterial level, the relative abundance of Rikenellaceae RC9 gut group, Christensenellaceae R7 group, Candidatus Saccharimonas, Desulfovibrio, and Lachnospiraceae FE2018 group decreased with RA supplementation. Conversely, the addition of RA significantly increased the relative abundance of DNF00809 (a genus from Eggerthellaceae), Denitrobacterium, an unclassified genus from Eggerthellaceae, an unclassified genus from Bacteroidales, and an unclassified genus from Atopobiaceae. At the archaeal level, the relative abundance of Methanobrevibacter decreased, while that of Methanosphaera increased with the RA supplementation. These findings suggested that RA has the potential to be used as a novel natural additive for inhibiting ruminal methane production.

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PURPOSE: Cinchoninze hydrochloride solves the problem of the low solubility of cinchonine, but it is unstable and susceptible to deliquescence. In this study, we designed and prepared cinchonine cocrystal salts or cinchonine salts with better stability, solubility and antioxidant activity than cinchonine. METHOD: We successfully synthesized and characterized three cinchonine salts, namely, cinchonine-fumaric acid, cinchonine-isoferulic acid, and cinchonine-malic acid. The high humidity (92.5% RH) and high temperature (60°C) tests were conducted to determine the physical stability and hygroscopicity of cinchonine hydrochloride, cinchonine and three cinchonine salts. And the ultraviolet spectrophotometry was conducted to determine the equilibrium solubility and intrinsic dissolution rate of cinchonine and salts. Moreover, the DPPH, ABTS, and FRAP assays determined the antioxidant activity of cinchonine and salts. RESULT: Compared with cinchonine hydrochloride and cinchonine, all three cinchonine salts exhibited good physical stability over 15 days under high humidity (92.5% RH) and high temperature (60°C) conditions. While cinchonine and cinchonine hydrochloride are categorized as hygroscopic and deliquescent, respectively, three cinchonine salts are classified as slightly hygroscopic, meaning that they have a lower hygroscopicity than cinchonine and cinchonine hydrochloride. And three cinchonine salts had higher equilibrium solubility, faster intrinsic dissolution rates, and higher antioxidant activity in comparison to cinchonine. Moreover, they showed a "spring and parachute" pattern in the phosphate buffer (pH = 6.8). CONCLUSION: Cocrystallization technology is a viable option for improving cinchonine's poor physicochemical qualities.

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OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

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OBJECTIVE: To establish an efficient nomogram model to predict short-term survival in ICU patients with aplastic anemia (AA). METHODS: The data of AA patients in the MIMIC-IV database were obtained and randomly assigned to the training set and testing set in a ratio of 7:3. Independent prognosis factors were identified through univariate and multivariate Cox regression analyses. The variance inflation factor was calculated to detect the correlation between variables. A nomogram model was built based on independent prognostic factors and risk scores for factors were generated. Model performance was tested using C-index, receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and Kaplan-Meier curve. RESULTS: A total of 1,963 AA patients were included. A nomogram model with 7 variables was built, including SAPS II, chronic pulmonary obstructive disease, body temperature, red cell distribution width, saturation of peripheral oxygen, age and mechanical ventilation. The C-indexes in the training set and testing set were 0.642 and 0.643 respectively, indicating certain accuracy of the model. ROC curve showed favorable classification performance of nomogram. The calibration curve reflected that its probabilistic prediction was reliable. DCA revealed good clinical practicability of the model. Moreover, the Kaplan-Meier curve showed that receiving mechanical ventilation could improve the survival status of AA patients in the short term but did not in the later period. CONCLUSION: The nomogram model of the short-term survival rate of AA patients was built based on clinical characteristics, and early mechanical ventilation could help improve the short-term survival rate of patients.

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The purpose of this study was to investigate the effects of feed ingredients with different protein-to-fat ratios on growth, slaughter performance and meat quality of Small-Tail Han lambs. Forty-five Small-Tail Han lambs (♂) (BW = 34.00 ± 2.5 kg, age = 120 ± 9 d) were randomly divided into groups with three different experimental treatments: (1) PF 5, with the ratio of protein to fat (CP:EE) of 50 to 5; (2) PF10, CP: EE = 50:10; (3) PF20, CP: EE = 50:20. Each treatment group had 15 lambs, and each sheep was a repeat. This experiment lasted for 65 days, with feed intake recorded daily, and animals being weighed on days 0, 30, and 65. At the conclusion of the experiment, eight lambs from each group were slaughtered to assess slaughter performance and meat quality. The results showed that the average daily gain (ADG) of the three groups were 315.27, 370.15 and 319.42 g/d, respectively. The PF10 group had the highest ADG (370.15 g) (p < 0.05). Forestomach weights (1216.88 g) of the PF10 group were significantly higher than those of the other groups (p < 0.05). There were no differences (p > 0.05) in fat percentages in various parts of body among treatments. Feed conversion of the PF10 group was higher (p < 0.05) than that of PF 5 and PF 20 groups. Furthermore, the PF10 group had a higher (p > 0.05) carcass weight and slaughter rate and there were few differences between the other groups in terms of dry matter intake, meat quality, organ weight, and fat deposition (p > 0.05). The protein-energy supplement with protein-to-fat ratio, PF10 appeared to be more desirable to promote the growth and development in Small-Tail Han Lambs.

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IMPORTANCE: Yaks, as ruminants inhabiting high-altitude environments, possess a distinct rumen microbiome and are resistant to extreme living conditions. This study investigated the microbiota, resistome, and functional gene profiles in the rumen of yaks fed milk or milk replacer (MR), providing insights into the regulation of the rumen microbiome and the intervention of antimicrobial resistance in yaks through dietary methods. The abundance of Prevotella members increased significantly in response to MR. Tetracycline resistance was the most predominant. The rumen of yaks contained multiple antimicrobial resistance genes (ARGs) originating from different bacteria, which could be driven by MR, and these ARGs displayed intricate and complex interactions. MR also induced changes in functional genes. The enzymes associated with fiber degradation and butyrate metabolism were activated and showed close correlations with Prevotella members and butyrate concentration. This study allows us to deeply understand the ruminal microbiome and ARGs of yaks and their relationship with rumen bacteria in response to different milk sources.

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BACKGROUND: Rumen bacterial groups can affect growth performance, such as average daily gain (ADG), feed intake, and efficiency. The study aimed to investigate the inter-relationship of rumen bacterial composition, rumen fermentation indicators, serum indicators, and growth performance of Holstein heifer calves with different ADG. Twelve calves were chosen from a trail with 60 calves and divided into higher ADG (HADG, high pre- and post-weaning ADG, n = 6) and lower ADG (LADG, low pre- and post-weaning ADG, n = 6) groups to investigate differences in bacterial composition and functions and host phenotype. RESULTS: During the preweaning period, the relative abundances of propionate producers, including g_norank_f_Butyricicoccaceae, g_Pyramidobacter, and g_norank_f_norank_o_Clostridia_vadinBB60_group, were higher in HADG calves (LDA > 2, P < 0.05). Enrichment of these bacteria resulted in increased levels of propionate, a gluconeogenic precursor, in preweaning HADG calves (adjusted P < 0.05), which consequently raised serum glucose concentrations (adjusted P < 0.05). In contrast, the relative abundances of rumen bacteria in post-weaning HADG calves did not exert this effect. Moreover, no significant differences were observed in rumen fermentation parameters and serum indices between the two groups. CONCLUSIONS: The findings of this study revealed that the preweaning period is the window of opportunity for rumen bacteria to regulate the ADG of calves.

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BACKGROUND: Ruminant livestock production is a considerable source of enteric methane (CH4) emissions. In a previous study, we found that dietary inclusions of Bacillus subtilis (BS) and Macleaya cordata extract (MCE) increased dry matter intake and milk production, while reduced enteric CH4 emission in dairy cows. The objective of this study was to further elucidate the impact of feeding BS and MCE on rumen methanogenesis in dairy cows using rumen metagenomics techniques. RESULTS: Sixty dairy cows were blocked in 20 groups of 3 cows accordingly to their live weight, milk yield, and days in milk, and within each group, the 3 cows were randomly allocated to 1 of 3 treatments: control diet (CON), control diet plus BS (BS), and control diet plus MCE (MCE). After 75 days of feeding experimental diets, 12 cows were selected from each treatment for collection of rumen samples for the metagenomic sequencing. Results showed that BS decreased ruminal acetate and butyrate, while increased propionate concentrations, resulting in decreased acetate:propionate ratio. The metagenomics analysis revealed that MCE reduced relative abundances of Methanobrevibacter wolinii, Methanobrevibacter sp. AbM4, Candidatus Methanomassiliicoccus intestinalis, Methanobrevibacter cuticularis, Methanomicrobium mobile, Methanobacterium formicicum, and Methanobacterium congolense. Both BS and MCE reduced relative abundances of Methanosphaera sp. WGK6 and Methanosphaera stadtmanae. The co-occurrence network analysis of rumen bacteria and archaea revealed that dietary treatments influenced microbial interaction patterns, with BS and MCE cows having more and stronger associations than CON cows. The random forest and heatmaps analysis demonstrated that the Halopenitus persicus was positively correlated with fat- and protein-corrected milk yield; Clostridium sp. CAG 269, Clostridium sp. 27 14, Haloarcula rubripromontorii, and Methanobrevibacter curvatus were negatively correlated with rumen acetate and butyrate concentrations, and acetate:propionate ratio, whereas Selenomonas rumiantium was positively correlated with those variables. CONCLUSIONS: The present results provided new information for mitigation of enteric methane emissions of dairy cows by feeding BS and MCE to influence rumen microbial activities. This fundamental knowledge is essential for developing enteric CH4 reduction strategies to mitigate climate change and reduce dietary energy waste. Video Abstract.

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The purpose of this experiment was to evaluate changes in fermentation quality, chemical composition, aerobic stability, anti-nutritional factors, and in situ disappearance characteristics of various protein-based total mixed rations. Soybean meal (control, non-fermented), fermented cottonseed meal (F-CSM), and fermented rapeseed meal (F-RSM) group were used to prepare the TMRs with corn, whole-plant corn silage, corn stalks, wheat bran, and premix. The test groups were inoculated at 50% moisture with Bacillus clausii and Saccharomyces cariocanus and stored aerobically for 60 h. The nylon-bag method was used to measure and study the rumen's nutrient degradation. The pH of all TMRs after 48 h of air exposure was below 4.8, whereas that of the F-CSM and control and F-RSM groups increased to 5.0 and >7.0, respectively. After 8 h of aerobic exposure, the temperatures of all groups significantly increased, and 56 h later, they were 2 °C higher than the surrounding air. The lactic acid concentration in the F-CSM and F-RSM groups increased after 12 h of aerobic exposure and then decreased. The acetic acid concentrations in the fermented groups decreased significantly with the increasing air-exposure time. The yeast population of the TMRs increased to more than 8.0 log10 CFU/g before 72 h of air exposure, followed by a decrease in the population (5.0 log10 CFU/g). After fermentation, the free gossypol (FG) concentration in F-CSM decreased by half and did not change significantly during the air-exposure period. Fermentation with probiotics also reduced the F-RSM's glucosinolate concentration, resulting in a more than 50% detoxification rate. Compared with the F-CSM and F-RSM groups, the effective degradation rates of nutrients in the control group were the lowest, and the dry matter (DM), crude protein (CP), natural detergent fiber (NDF), and acid detergent fiber (ADF) all degraded effectively at rates of 28.4%, 34.5%, 27.8%, and 22.8%, respectively. Fermentation with B. clausii and S. cariocanus could improve the fermentation quality and nutrient composition, decrease the anti-nutritional factor, and increase nutrient degradation of the TMR with cottonseed meal or rapeseed meal as the main protein source, thus achieving detoxification.

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Colorectal cancer (CRC) remains a significant global health issue. In this study, the role of T-cell exhaustion-related genes (TEXs) in CRC was investigated using single-cell and bulk RNA-seq analysis. This research involved extensive data analysis using multiple databases, including the TCGA-COAD cohort, GSE14333, and GSE39582. Through single-cell analysis, distinct cell populations within CRC samples were identified and classified T-cells into four subgroups: regulatory T-cells (Tregs), conventional CD4+ T-cells (CD4+ T conv), CD8+ T, and CD8+ T exhausted cells. Intercellular communication networks and signaling pathways associated with TEXs using computational tools such as CellChat and PROGENy. Additionally, TEX-related alterations in tumor gene pathways were analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Prognostic models were developed, and their correlation with immune infiltration was assessed. The study revealed the presence of distinct cell populations within CRC, with TEXs playing a crucial role in the tumor microenvironment. CD8+ T exhausted cells exhibited expression of specific markers, indicating their involvement in tumor immune evasion. CellChat and PROGENy analyses revealed intricate communication networks and signaling pathways associated with TEXs, including RNA splicing and viral carcinogenesis. Furthermore, the prognostic risk model developed on the basis of TEXs demonstrated its efficacy in stratifying CRC patients. This risk model exhibited strong correlations with immune infiltration by various effector immune cells, highlighting the influence of TEXs on the tumor immune response. The complex interactions and signaling pathways underlying TEX-associated immune dysregulation in CRC were revealed by employing advanced analytical approaches. The development of a prognostic risk model based on TEXs offers a promising tool for prognostic stratification in patients with CRC. Furthermore, the correlations observed between TEXs and immune infiltration provide valuable insights into the potential of TEXs as therapeutic targets and highlight the need for further investigation into TEX-mediated immune evasion mechanisms. This study thus provides valuable insights into the role of TEXs in CRC.

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The goal of this study was to investigate Candida tropicalis as a kind of environmentally friendly dietary additive to manipulate ruminal fermentation patterns, reduce methane emissions and nitrogen excretion, and to screen the appropriate dose for sheep. Twenty-four Dorper × thin-tailed Han crossbred ewes (51.12 kg ± 2.23 kg BW) were selected and randomly divided into four groups which were fed Candida tropicalis at dose of 0 (control), 4 × 108 (low dose), 4 × 109 (medium dose), and 4 × 1010 (high dose) colony-forming units (CFU)/d per head, respectively. The experiment lasted 33 days with 21 days for adaptation and 12 days for nutrient digestibility trial and respiratory gases sampling. The results showed that nutrients intake was not affected by Candida tropicalis supplementation (P > 0.05), whereas apparent digestibility of nutrients significantly increased compared with the control group (P < 0.05). Nitrogen and energy utilization increased with Candida tropicalis supplementation (P < 0.05). Compared with the ewes of the control group, rumen fluid pH and NH3-N concentration were not affected (P > 0.05), whereas total volatile fatty acid concentration and molar proportion of propionate were greater (P < 0.05), and molar proportion of acetate and the ratio of acetate to propionate were less (P < 0.05) when the ewes were fed Candida tropicalis. Daily total CH4 production (L/d) and CH4 emissions yield (L/d of CH4 per kg of dry matter intake, metabolic weight, or digestibility dry matter intake) were decreased at the low dose group (P < 0.05). The abundance of total bacteria, methanogen, and protozoa in rumen fluid was significantly higher at medium dose and high dose of Candida tropicalis supplementation (P < 0.05) compared with low dose and the control group. In summary, Candida tropicalis supplementation has a potential to reduce CH4 emissions and nitrogen excretion, and the optimal dose should be 4 × 108 CFU/d per head.

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