Search

Rumen-protected methionine (RPM) such as coated methionine (CM) and 2-hydroxy-4-(methylthio)-butanoic acid isopropyl ester (HMBi) was usually used in dairy cows, but how RPM affects meat goats remains unclear. In this study, thirty weaned male Jianzhou Da'er goats were randomly assigned to one of three treatments: fed basal diet or basal diet supplemented with 0.12% CM or 0.22% HMBi, with the aim of examining their impact on growth performance, serum biochemistry, rumen fermentation, rumen microbiota, and intestinal development in meat goats. The findings indicate that HMBi supplementation led to an increase in body weight, feed intake, and feed-to-gain ratio, whereas CM only resulted in an increase in feed intake (all p < 0.05). Both CM and HMBi resulted in an increase in serum total cholesterol (TC), blood urea nitrogen (BUN), alkaline phosphatase (ALP), and aspartate aminotransferase (AST), albeit with a decrease in serum triglycerides (TG) and β -hydroxybutyric acid (BHB, all p < 0.05). Both CM and HMBi supplementation decreased the rumen butyric acid concentration (both p < 0.05). The 16S rRNA sequencing showed that HMBi supplementation significantly increased the total abundance of Bacteroidetes and Firmicutes. Both CM and HMBi supplements increased the abundance of Rikenella and Proteiniphilum but decreased the abundance of Eisenbergiella , Enterocloster , Massilioclostridium , Eubacterium , Angelakisella , Blastopirellula , Christensenella, and Pseudoruminococcus. CM supplementation specifically increased the abundance of Desulfobulbus , Sodaliphilus, and Coprococcus while decreasing the prevalence of Anaerocella , Mogibacterium, and Collinsella. The supplementation of HMBi significantly enhanced the abundance of Paraprevotella , Bacilliculturomica , Lachnoclostridium , Dysosmobacter , Barnesiella , and Paludibacter , while decreasing the abundance of Butyrivibrio and Pirellula. Moreover, the administration of both CM and HMBi supplementation resulted in an increase in the ammonia-producing and sulfate-reducing bacteria, whereas a decrease was observed in the ammonia-oxidating, health-associated, and disease-associated bacteria. Correlational analysis revealed that TG and BHB had a positive correlation with disease-associated and ammonia-oxidating bacteria, whereas they had a negative correlation with ammonia-producing bacteria. The serum BUN, ALP, and AST were positively correlated with ammonia-producing bacteria but were negatively correlated with ammonia-oxidating bacteria. Furthermore, both CM and HMBi supplementation improve the development of the small intestine, with HMBi having a better effect. In summary, this study indicates that both CM and HMBi supplementation improve lipid metabolism, nitrogen utilization, and intestinal development. The growth promotion effect of HMBi supplementation may be attributed to the increased abundance of volatile fatty acid-producing and nitrogen-utilizing bacteria and improved intestinal development. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the pharmacokinetics (PKs) and safety of a generic drug, linezolid, compared to those of a reference drug in healthy Chinese subjects under both fasting and fed conditions. This was a randomized, open‐label, 2‐period, 2‐sequence crossover study. The subjects received a single dose of the test or reference drug, linezolid (600 mg), in each period. The PK parameters were calculated using a non‐compartmental method and compared between the 2 drugs. Bioequivalence was analyzed using geometric mean ratios (GMRs) of the 2 formulations and their corresponding 90% confidence intervals (CIs). The safety of the 2 formulations was assessed under both fasting and fed conditions. Forty‐eight subjects completed the study, 24 each in the fasting and feeding groups. The average plasma concentration‐time patterns of linezolid were similar for both medications under both conditions. The GMR and 90% CIs of the maximum plasma concentration and the area under the plasma concentration‐time curve of linezolid were ranged from 0.80 to 1.25. Both drugs were well tolerated with a similar incidence of adverse drug reactions. In conclusion, the PK and safety profiles of the 2 formulations were comparable. Food intake did not influence the PK profiles of linezolid. These results suggest that the test drug can be used as an alternative to reference drugs. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The construction of acyclic quaternary carbon stereocenters, which are ubiquitous in many bioactive compounds, pharmaceuticals and natural products, has been a long persuit in synthetic organic chemistry. Among numerous methods, enantioselective nickel‐catalysis has attracted incremental attention in recent years. This review summarizes the recent development in the asymmetric strategies, research progress, mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis. Key Scientists: In 2006, the Zhou group and RajanBabu group realized the nickel‐catalyzed enantioselective hydrovinylation of α‐substituted styrenes and ethylene to construct acyclic quaternary carbon stereocenters (QCSs) by using spiro‐ and binaphthyl phosphoramidite ligands, respectively. In 2016, Watson developed a nickel‐catalyzed Suzuki‐Miyaura arylation to generate acyclic QCSs via chirality transfer reaction. In 2017, the Feng and the Fu group developed nickel‐catalyzed enantioselective conjugated/Michael additions to build acyclic QCSs, respectively. In 2020, the Fang group made the first success in the construction of QCSs by nickel‐catalyzed hydrocyanation of alkenes and allenes. In 2021, Gregory C. Fu and co‐workers disclosed a nickel‐catalyzed enantioselective α‐functionalization of carbonyl compounds that could form acyclic QCSs. At the same time, the Shi group constructed chiral acyclic QCSs via nickel‐catalyzed functionalization of alkenes. In 2023, Kleij and co‐workers applied a new strategy for Ni‐catalyzed regio‐ and enantioselective homoallylic coupling to construct acyclic QCSs. In the same year, Tao and co‐workers demonstrated a novel strategy that is dinickel‐catalyzed enantioselective α‐alkylation of carbonyl compounds with alkyl iodides. [ABSTRACT FROM AUTHOR]

Nickel‐catalyzed asymmetric intramolecular addition of aryl halides to α‐ketoamides has been achieved to afford chiral 3‐substituted‐3‐hydroxy‐2‐oxindoles in excellent yields and high enantioselectivities (up to 99 % yield and 98 % ee), which provides efficient access to valuable molecules containing 3‐hydroxy‐2‐oxindole core. The gram‐scale reaction proved the potential utility of the methodology. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The construction of acyclic quaternary carbon stereocenters, which are ubiquitous in many bioactive compounds, pharmaceuticals and natural products, has been a long persuit in synthetic organic chemistry. Among numerous methods, enantioselective nickel‐catalysis has attracted incremental attention in recent years. This review summarizes the recent development in the asymmetric strategies, research progress, mechanistic investigations for the generation of acyclic quaternary carbon stereocenters via enantioselective nickel catalysis. Key Scientists: In 2006, the Zhou group and RajanBabu group realized the nickel‐catalyzed enantioselective hydrovinylation of α‐substituted styrenes and ethylene to construct acyclic quaternary carbon stereocenters (QCSs) by using spiro‐ and binaphthyl phosphoramidite ligands, respectively. In 2016, Watson developed a nickel‐catalyzed Suzuki‐Miyaura arylation to generate acyclic QCSs via chirality transfer reaction. In 2017, the Feng and the Fu group developed nickel‐catalyzed enantioselective conjugated/Michael additions to build acyclic QCSs, respectively. In 2020, the Fang group made the first success in the construction of QCSs by nickel‐catalyzed hydrocyanation of alkenes and allenes. In 2021, Gregory C. Fu and co‐workers disclosed a nickel‐catalyzed enantioselective α‐functionalization of carbonyl compounds that could form acyclic QCSs. At the same time, the Shi group constructed chiral acyclic QCSs via nickel‐catalyzed functionalization of alkenes. In 2023, Kleij and co‐workers applied a new strategy for Ni‐catalyzed regio‐ and enantioselective homoallylic coupling to construct acyclic QCSs. In the same year, Tao and co‐workers demonstrated a novel strategy that is dinickel‐catalyzed enantioselective α‐alkylation of carbonyl compounds with alkyl iodides. [ABSTRACT FROM AUTHOR]

The aim of this study was to elucidate the effect of FAM13A on the differentiation of goat intramuscular precursor adipocytes and its mechanism of action. Here, we cloned the CDS region 2094 bp of the goat FAM13A gene, encoding a total of 697 amino acid residues. Functionally, overexpression of FAM13A inhibited the differentiation of goat intramuscular adipocytes with a concomitant reduction in lipid droplets, whereas interference with FAM13A expression promoted the differentiation of goat intramuscular adipocytes. To further investigate the mechanism of FAM13A inhibiting adipocyte differentiation, 104 differentially expressed genes were screened by RNA-seq, including 95 up-regulated genes and 9 down-regulated genes. KEGG analysis found that the RIG-I receptor signaling pathway, NOD receptor signaling pathway and toll-like receptor signaling pathway may affect adipogenesis. We selected the RIG-I receptor signaling pathway enriched with more differential genes as a potential adipocyte differentiation signaling pathway for verification. Convincingly, the RIG-I like receptor signaling pathway inhibitor (HY-P1934A) blocked this pathway to save the phenotype observed in intramuscular adipocyte with FAM13A overexpression. Finally, the upstream miRNA of FAM13A was predicted, and the targeted inhibition of miR-21-5p on the expression of FAM13A gene was confirmed. In this study, it was found that FAM13A inhibited the differentiation of goat intramuscular adipocytes through the RIG-I receptor signaling pathway, and the upstream miRNA of FAM13A (miR-21-5p) promoted the differentiation of goat intramuscular adipocytes. This work extends the genetic regulatory network of IMF deposits and provides theoretical support for improving human health and meat quality from the perspective of IMF deposits. [ABSTRACT FROM AUTHOR]

In this paper, we report a 12-week longitudinal study aiming at exploring the students' reading outcome and cognitive load with individual-based print, mobile app of Rain Classroom and collaboration-based social media of WeChat. Administered to 186 postgraduate students in a research university were the weekly reading materials and comprehension tests, together with the self-designed CLCR scale after the reading sessions. A combination of one-way and repeated measures ANOVA along with multi-regression analysis showed that social media produced the best reading outcome; The same pattern occurred about enhanced reading outcome in the initial sessions followed by a decline at the end; Reading outcome in print other than in mobile and social media significantly increased from the first session to the ending session; Reading in mobile generated the highest level of extraneous, intrinsic, and germane load; Multi-regression analysis showed a negative relationship between intrinsic load and the prediction of collaborative reading across all the reading contexts. Further efforts may contribute to more complex patterns of reading outcome and cognitive load status by arranging individual- and collaboration-based contexts in different sequences for students with high and low level of cognitive load. [ABSTRACT FROM AUTHOR]

Accurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA cohort, including the baseline S4 and follow-up F4 studies, consisting of 1454 participants without prior history of MI. The dataset comprised 19 clinical variables and 363 metabolites. Due to the imbalanced nature of the dataset (78 observed MI cases and 1376 non-MI individuals), we employed a generative adversarial network (GAN) model to generate new incident cases, augmenting the dataset and improving feature representation. To predict MI, we further utilized multi-layer perceptron (MLP) models in conjunction with the synthetic minority oversampling technique (SMOTE) and edited nearest neighbor (ENN) methods to address overfitting and underfitting issues, particularly when dealing with imbalanced datasets. To enhance prediction accuracy, we propose a novel GAN for feature-enhanced (GFE) loss function. The GFE loss function resulted in an approximate 2% improvement in prediction accuracy, yielding a final accuracy of 70%. Furthermore, we evaluated the contribution of each clinical variable and metabolite to the predictive model and identified the 10 most significant variables, including glucose tolerance, sex, and physical activity. This is the first study to construct a deep-learning approach for producing 7-year MI predictions using the newly proposed loss function. Our findings demonstrate the promising potential of our technique in identifying novel biomarkers for MI prediction. [ABSTRACT FROM AUTHOR]