GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

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.

Enhancing the Stability, Solubility, and Antioxidant Activity of Cinchonine through Pharmaceutical Cocrystallization.

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.

Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study.

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.

In-Silico and in vitro Studies Revealed that Rosmarinic Acid Inhibited Methanogenesis via Regulating Composition and Function of Rumen Microbiota.

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.

Photodetector with a metalens packaging module for visible light communication based on RGBY illumination LED light source.

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.

Nomogram establishment for short-term survival prediction in ICU patients with aplastic anemia based on the MIMIC-IV database.

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.

Effects of Feed Ingredients with Different Protein-to-Fat Ratios on Growth, Slaughter Performance and Fat Deposition of Small-Tail Han Lambs.

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.

Altered microbiota, antimicrobial resistance genes, and functional enzyme profiles in the rumen of yak calves fed with milk replacer.

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.

Preweaning period is a critical window for rumen microbial regulation of average daily gain in Holstein heifer calves.

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.

Bacillus subtilis and Macleaya cordata extract regulate the rumen microbiota associated with enteric methane emission in dairy cows.

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.

Evaluating Fermentation Quality, Aerobic Stability, and Rumen-Degradation (In Situ) Characteristics of Various Protein-Based Total Mixed Rations.

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.

Elucidating the role of T-cell exhaustion-related genes in colorectal cancer: a single-cell bioinformatics perspective.

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.

Candida tropicalis as a novel dietary additive to reduce methane emissions and nitrogen excretion in sheep.

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.

Interaction between microorganisms and dental material surfaces: general concepts and research progress.

Bacterial adhesion to dental materials' surfaces is the initial cause of dental materials-related infections. Therefore, inhibiting bacterial adhesion is a critical step in preventing and controlling these infections. To this end, it is important to know how the properties of dental materials affect the interactions between microorganisms and material surfaces to produce materials without biological contamination. This manuscript reviews the mechanism of bacterial adhesion to dental materials, the relationships between their surface properties and bacterial adhesion, and the impact of bacterial adhesion on their surface properties. In addition, this paper summarizes how these surface properties impact oral biofilm formation and proposes designing intelligent dental material surfaces that can reduce biological contamination.

Advances in the Application of Phytogenic Extracts as Antioxidants and Their Potential Mechanisms in Ruminants.

Under current breeding conditions, multiple stressors are important challenges facing animal husbandry in achieving animal wellbeing. For many years, the use of antibiotics has been a social concern in the livestock industry. With the implementation of the non-antibiotics policy, there is an urgent need to find relevant technologies and products to replace antibiotics and to solve the problem of disease prevention during animal growth. Phytogenic extracts have the unique advantages of being natural and extensive sources, having a low residue, and being pollution-free and renewable. They can relieve the various stresses, including oxidative stress, on animals and even control their inflammation by regulating the signaling pathways of proinflammatory cytokines, improving animal immunity, and improving the structure of microorganisms in the gastrointestinal tract, thereby becoming the priority choice for improving animal health. In this study, we reviewed the types of antioxidants commonly used in the livestock industry and their applicable effects on ruminants, as well as the recent research progress on their potential mechanisms of action. This review may provide a reference for further research and for the application of other phytogenic extracts and the elucidation of their precise mechanisms of action.

Fermented cottonseed and rapeseed meals outperform soybean meal in improving performance, rumen fermentation, and bacterial composition in Hu sheep.

Background: This study examined the effects of substituting cottonseed meal (CSM) or rapeseed meal (RSM) for soybean meal (SBM) on Hu sheep performance, rumen fermentation, and bacterial composition. 51 four-month-old indigenous male Hu sheep with starting body weights of 22.51 ± 2.84 kg and similar origins were randomly assigned to three treatments; (1) non-fermented total mixed ration (TMR) with SBM (CK), (2) fermented TMR containing CSM (F-CSM group), and (3) fermented TMR containing RSM (F-RSM group). Results: The three groups' intake of dry matter differed significantly (p < 0.05). In terms of average daily gain, the F-RSM group outperformed the CK and F-CSM groups (p < 0.05). The pH of the rumen was substantially lower in the CK group than in the F-CSM and F-RSM groups (p < 0.05), and the F-CSM group had greater amounts of volatile fatty acids (VFA) than the F-RSM and CK groups. In comparison to the CK group, the microbial crude protein yield was significantly higher in the F-CSM and F-RSM groups (p < 0.05). The F-CSM group significantly outperformed the F-RSM group of pepsin and cellulose enzyme activity (p < 0.05). The relative abundance of Bacteroidetes was greater in the CK and F-RSM groups compared to the F-CSM group (p < 0.05). In comparison to the other groups, Firmicutes were less abundant in the CK group (p < 0.05). Prevotella was present in a higher relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). Prevotella was greater in relative abundance in the F-CSM and F-RSM groups than in the CK group (p < 0.05). The relative abundances of Veillonellaceae_UCG-001 and Lachnospiraceae_XPB1014 correlated with rumen butyric acid content and NH3-N content (p < 0.05). Gene function prediction revealed that replacing SBM with F-CSM or F-RSM in the diet of Hu sheep can promote glycan biosynthesis and metabolism. Conclusion: The replacement of F-CSM and F-RSM for SBM has an influence on the richness and diversity of rumen bacteria at the phylum and genus levels. Replacement of SBM with F-CSM increased VFA yield and further promoted the performance of Hu sheep.

Characterization of the Dynamic Changes of Ruminal Microbiota Colonizing Citrus Pomace Waste during Rumen Incubation for Volatile Fatty Acid Production.

Rumen microorganisms are promising for efficient bioconversion of lignocellulosic wastes to biofuels and industrially relevant products. Investigating the dynamic changes of the rumen microbial community colonizing citrus pomace (CtP) will advance our understanding of the utilization of citrus processing waste by rumen fluid. Citrus pomace in nylon bags was incubated in the rumen of three ruminally cannulated Holstein cows for 1, 2, 4, 8, 12, 24, and 48 h. Results showed that total volatile fatty acids concentrations and proportions of valerate and isovalerate were increased over time during the first 12 h. Three major cellulose enzymes attached to CtP rose initially and then decreased during the 48-h incubation. Primary colonization happened during the initial hours of CtP incubation, and microbes compete to attach CtP for degrading easily digestible components and/or utilizing the waste. The 16S rRNA gene sequencing data revealed the diversity and structure of microbiota adhered to CtP were distinctly different at each time point. The increased abundance of Fibrobacterota, Rikenellaceae_RC9_gut_group, and Butyrivibrio may explain the elevated volatile fatty acids concentrations. This study highlighted key metabolically active microbial taxa colonizing citrus pomace in a 48-h in situ rumen incubation, which could have implications for promoting the biotechnological process of CtP. IMPORTANCE As a natural fermentation system, the rumen ecosystem of ruminants can efficiently degrade plant cellulose, indicating that the rumen microbiome offers an opportunity for anaerobic digestion to utilize biomass wastes containing cellulose. Knowledge of the response of the in situ microbial community to citrus pomace during anaerobic fermentation will help improve the current understanding of citrus biomass waste utilization. Our results demonstrated that a highly diverse rumen bacterial community colonized citrus pomace rapidly and continuously changed during a 48-h incubation period. These findings may provide a deep understanding of constructing, manipulating, and enriching rumen microorganisms to improve the anaerobic fermentation efficiency of citrus pomace.

Effects of Two Feeding Patterns on Growth Performance, Rumen Fermentation Parameters, and Bacterial Community Composition in Yak Calves.

The health of young ruminants is highly dependent on early rumen microbial colonization. In this study, the effects of milk replacer on growth performance, rumen fermentation, and the rumen microflora in yak calves were evaluated. Sixty yak calves (body weight = 22.5 ± 0.95 kg, age = 30 ± 1 d) were assigned to the CON group (breastfed) or TRT group (milk replacer fed) and evaluated over 120 d. At 120 d, ruminal fluid samples were collected from 14 calves and then conducted for rumen fermentation and microbiota analyses. There was no difference in growth performance; however, calf survival was higher in the TRT group than in the CON group. The concentration of total volatile fatty acids and the molar proportion of butyric acid and lactic acid were increased with milk replacer feed in the TRT group (p < 0.05), but iso-valeric acid concentration was highest in the CON group (p < 0.05). Firmicutes and Bacteroidetes were the most dominant phyla in the CON and TRT groups, respectively. In the TRT group, Bacteroidetes, Prevotellaceae, Bacteroidia, Bacteroidetes, and Prevotella_1 were the dominant flora in the rumen of calves. The relative abundances of various taxa were correlated with rumen fermentation parameters; the relative abundance of Quinella and iso-butyrate levels were positively correlated (r = 0.57). The relative abundances of the Christensenellaceae_R-7_group and A/P were positively correlated (r = 0.57). In summary, milk replacer is conducive to the development of the rumen microflora, the establishment of rumen fermentation function, and the implementation of early weaning in yaks.

Effects of Coconut Oil and Palm Oil on Growth, Rumen Microbiota, and Fatty Acid Profile of Suckling Calves.

This study aimed to evaluate the effects of coconut oil and palm oil in milk replacer (MR) on the growth performance, blood lipids, rumen fermentation, rumen microbiota, and fatty acid profile of hepatic and muscle of suckling calves. Thirty-six Holstein male calves were randomly assigned to three treatments. Three milk replacers containing different fat sources were as follows: control group (CON, milk fat), coconut oil group (CCO, coconut oil powder as fat), and palm oil group (PLO, palm oil powder as fat). Calves were weighed and blood sampled at 14, 28, 42, and 56 days old, respectively, and the feed intake and fecal score were recorded daily. Fat sources in milk replacers had no effects on body weight, ADG, DMI, fecal score, or days of abnormal fecal in suckling calves among the three groups, while the PLO group tended to decrease starter intake compared with the other groups. Serum concentrations of TC, HDL-C, LDL-C, and VLDL-C in the CCO group increased compared with those of the CON group. Palm oil also decreased the serum GLU concentration of calves but had no effects on serum lipids compared with milk fat. Coconut oil or palm oil had no effects on rumen fermentation, rumen chyme enzyme activity, rumen bacterial community richness and diversity, and dominant phyla and genera when compared with milk fat. However, compared with the CON group, the CCO group increased the proportion of MCFAs and n-6 PUFAs, and decreased the proportion of UFAs and MUFAs in liver tissue, while the PLO group increased the proportion of PUFAs and decreased the proportion of n-3 PUFAs in liver tissue. In addition, compared with the CON group, the CCO group increased the proportion of MCFAs, and decreased the proportion of UFAs and n-3 PUFAs in longissimus dorsi, while the PLO group increased the proportion of PUFAs and decreased the proportion of n-3 PUFAs in longissimus dorsi. In conclusion, compared with milk fat, coconut oil or palm oil in MR had no effects on growth performance, rumen fermentation, and rumen microflora but significantly increased serum lipids concentration and changed some proportions of MCFAs and PUFAs in liver and longissimus dorsi in suckling calves. These results indicate that coconut oil or palm oil as the sole fat source for MRs has no adverse effect on calf rumen fermentation and rumen microbiota but has a detrimental effect on n-3 PUFAs deposition in the liver and longissimus dorsi muscle.

Related donor platelet transfusion improves platelet transfusion refractoriness in hematological patients.

Objective: Transfusion of HLA-matched platelets can reduce the effect of alloimmune responses on platelet transfusion efficacy; however, finding HLA-matched platelets in the population is nearly impossible. Almost all HLA-matched platelets from related are half-matched, but the hemostatic efficacy of related donor platelets is unclear. Our goal was to compare the hemostatic effect of related donated platelets and unrelated donors platelets. Methods: In this retrospective cohort study, we included acute leukemia and myelodysplastic syndrome patients with thrombocytopenia after chemotherapy. These patients were all transfused with platelets. This study excluded patients younger than 16 years and older than 65 years, or patients with abnormal coagulation parameters during platelet transfusion. We compared the hemostatic effect of related donated platelets and unrelated donors platelet. The primary outcome was transfusion efficacy after platelet transfusion, and the number of platelet counts and corrected count increments at 24 h after platelet transfusion. Result: We analyzed 31 patients who received platelet transfusions from related donors (Treatment group) and 35 patients who received platelet transfusions from unrelated donors (Comparator group). Except for the relatively small proportion of patients with myelodysplastic syndrome in the treatment group, baseline clinical and laboratory characteristics were similar between the two groups. Hemostasis and prevention of bleeding in the treatment group showed significant superiority; the number of platelets increased 24 h after platelet transfusion in the treatment group was significantly higher than that in the comparator group. After 24 h, the corrected count increments treatment group was also higher than the comparator group; in the treatment group, the transfusion effect was better when the three sites of HLA-A, B, and C were identical, and the different blood types of platelet donors and recipients did not affect the transfusion effect. Conclusion: Related donated platelets have better hemostasis and prevention effects, and no increase in adverse blood transfusion reactions. It may be a better transfusion strategy for platelet refractoriness patients in emergency situations.