Ruminant rumen plays an important role in the digestibility of cellulose, hemicellulose, starch and fat. In this study, the yaks under graze and stall feeding were chosen as the models of different ...rumen bacteria and intramuscular fat (IMF). The characteristics of IMF deposition, serum indexes in yaks were detected; the bacteria, metabolites in rumen was explored by 16S rRNA sequencing technology, untargeted metabolomics based on liquid chromatography-mass spectrometer and gas chromatography, respectively; the transcriptome of longissimus thoracis was identified by RNA-Sequencing analysis. Based on above results, a hypothesis that yak IMF deposition is regulated by the combined action of microbiome-gut-brain and muscle axis was proposed. The short-chain fatty acids (SCFAs) and neurotransmitters precursors like acetylcholine produced in yak rumen promoted insulin secretion via central nervous system. These insulin resulted in the high expression of SREBF1 gene by gut-brain axis; SCFAs can directly arrive to muscular tissue via blood circulation system, then activated the expression of PPARγ gene by gut-muscle axis. The expression of lipogenesis gene SCD, FABP3, CPT1, FASN and ACC2 was accordingly up-regulated. This study firstly introduce the theory of microbiome-gut-brain/muscle axis into the study of ruminant, and comprehensively expounded the regulatory mechanism of yak IMF deposition.
•Microbial-gut-muscle and brain axis in livestock were verified for the frist time.•The insulin secretion via CNS was increased under the regulation of gut-brain axis mediated by SCFAs and neurotransmitters from the microbial fermentation in yaks rumen.•SCFAs also directly arrive to muscular tissue by blood circulation system via gut-muscle axis.•The up-regulated expression of lipogenesis gene PPARγ, SREBF1, SCD, FABP3, CPT1, FASN and ACC2 promotes IMF fat deposition in yaks.•Microbial-gut-muscle and brain axis also regulate the fatty acids composition in yak IMF.
The variety of species can be efficiently increased by interspecific hybridization. However, because the males in the hybrid progeny are usually sterile, this heterosis cannot be employed when other ...cattle and yaks are hybridized. While some system-level studies have sought to explore the etiological basis for male cattle-yak sterility, no systematic cellular analyses of this phenomenon have yet been performed. Here, single-cell RNA sequencing and UPHLC-MS/MS targeted metabolomics methods were used to study the differences in testicular tissue between 4-year-old male yak and 4-year-old male cattle-yak, providing new and comprehensive insights into the causes of male cattle-yak sterility. Cattle-yak testes samples detected 6 somatic cell types and one mixed germ cell type. Comparisons of these cell types revealed the more significant differences in Sertoli cells (SCs) and Leydig cells and myoid cells (LCs_MCs) between yak and cattle-yak samples compared to other somatic cell clusters. Even though the LCs and MCs from yaks and cattle-yaks were derived from the differentiation of the same progenitor cells, a high degree of overlap between LCs and MCs was observed in yak samples. Still, only a small overlap between LCs and MCs was observed in cattle-yak samples. Functional enrichment analyses revealed that genes down-regulated in cattle-yak SCs were primarily enriched in biological activity, whereas up-regulated genes in these cells were enriched for apoptotic activity. Furthermore, the genes of up-regulated in LCs_MCs of cattle-yak were significantly enriched in enzyme inhibitor and molecular function inhibitor activity. On the other hand, the genes of down-regulated in these cells were enriched for signal receptor binding, molecular function regulation, positive regulation of biological processes, and regulation of cell communication activity. The most significant annotated differences between yak and cattle-yak LCs_MCs were associated with cell-to-cell communication. While yak LCs_MCs regulated spermatogenic cells at spermatogonia, spermatocyte, and spermatid levels, no such relationships were found between cattle-yak LCs_MCs and germ cells. This may suggest that the somatic niche in male cattle-yak testes is a microenvironment that is ultimately not favorable for spermatogenesis.
Abstract To date, SARS‐CoV‐2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)‐approved ...repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID‐19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID‐19 patients, including 19 patients with severe disease. Among the 39 FDA‐approved drugs we identified for COVID‐19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID‐19 clinical trials and 9 drugs reported for COVID‐19 treatments, suggesting the remaining 16 FDA‐approved drugs may be candidates for COVID‐19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID‐19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID‐19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID‐19 treatment in poly(I:C)‐stimulated human non‐small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID‐19 remedies using FDA‐approved repurposed drugs and herbal sRNAs from TCMs.
La2Sn2O7/SnO2 powder was synthesized by chemical co-precipitation method, and Ag-La2Sn2O7/SnO2 composites were prepared by hot-pressing sintering. The electrical resistivity, density, Brinell ...hardness and flexural strength of Ag-La2Sn2O7/SnO2 composites were measured. Moreover, the effect of La2Sn2O7 content on the arc erosion behavior of Ag-La2Sn2O7/SnO2 composites at 7 kV voltage was studied. With the increase of La2Sn2O7 content, the arc duration and arc energy decrease, and the breakdown strength increases. The surface morphology of Ag-La2Sn2O7/SnO2 composites after arc erosion was investigated using scanning electron microscopy and three-dimensional laser confocal scanning microscopy. With the increase of La2Sn2O7 content, the smaller the erosion damage, the better the anti-arc erosion performance. However, too much La2Sn2O7 results in the decrease of Ag-La2Sn2O7/SnO2 properties and severe arc erosion. X-ray photoelectron spectroscopy was used to determine the composition of the erosion region. The effect of La2Sn2O7 on wettability between Ag and SnO2 was investigated, and the erosion mechanism of Ag-La2Sn2O7/SnO2 composites was discussed systematically. This study can provide a reference for the application of Ag matrix electrical contact materials in high-voltage electrical appliances.
Schematic illustration for preparation and arc erosion test of Ag-La2Sn2O7/SnO2 composites. La2Sn2O7 can improve the physical, mechanical and anti-arc erosion properties of the composites. Ag-La2Sn2O7/SnO2 composites are expected to be employed as electrical contact materials. Display omitted
•We investigated the effect of La2Sn2O7 content on the high-voltage arc erosion behavior of Ag-La2Sn2O7/SnO2 composites.•With the increase of La2Sn2O7 content, the arc duration and arc energy decrease, and the breakdown strength increases.•La2Sn2O7 can improve the wettability between Ag and SnO2, and reduce the splashing of the Ag droplets.•The decomposition of La2Sn2O7 can absorb a large amount of heat and reduce the arc energy.
Currently, two distinct lineages of influenza B virus (IBV), B/Victoria and B/Yamagata lineage, have been co‐circulating in human beings. Assessment of the prevalent lineage is key for the ...recommendation of the seasonal influenza vaccine composition and the evaluation of its efficacy. In this study, a multiplex qRT‐PCR assay for the discrimination of the IBV lineages was designed based on the genetic differences of the hemagglutinin genes between B/Yamagata and B/Victoria lineages. The assay was highly specific and able to discriminate the lineages of IBV without any non‐specific reaction against other influenza A viruses. The detection limit of the assay was determined to be 10 genome‐equivalent copies and 2.8 × 10‐2 50% tissue culture infectious doses (TCID50) of live IBV per reaction. Moreover, our assay was able to discriminate the lineages of IBVs in clinical samples with 100% accuracy, when compared with pyrosequencing. Our results indicate that this assay may represent an update of the existing qRT‐PCR assays and will be of great use for the rapid and accurate diagnosis and surveillance of the circulating IBVs.
Highlights
A multiplex qRT‐PCR assay was developed to discriminate the lineages of IBV with high sensitivity and broad coverage.
The detection limit of the assay was determined to be 10 genome‐equivalent copies and 2.8 × 10‐2 50% tissue culture infectious doses (TCID50) of live IBV.
This assaywill be of great use for the rapid and accurate diagnosis andsurveillance of the circulating IBVs.
This study aims to explore the key metabolites and metabolic pathways related to the formation of flavor in yak meat, laying the foundation for in-depth analysis of the composition of yak meat and ...improving meat quality. This study selected six healthy 4-year-old male Tianzhu white yaks under the same growth conditions as the research subjects. The metabolites of three groups of longissimi dorsi (LD), triceps brachii (TB), and biceps femoris (BF) were analyzed and identified using gas chromatography–ion mobility spectrometry (GC-IMS), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that Tianzhu white yak meat contains abundant metabolites, and the VOC levels in BF muscles are higher than those in LD and TB muscles. The levels of 1-penten-3-one and 2-pentone in LD muscle are higher than in BF and TB muscle. The levels of 2-hexanol, 2-hexanol-D, and pyridine in TB muscles are higher than those in LD and BF muscles. The content of benzaldehyde, benzaldehyde D, 3-hydroxy-2-butane-D, 3-hydroxy-2-butanone, and mesitylene in BF muscle is higher than in LD and TB muscle. There is a significant difference in the enrichment degree of the glycolysis or gluconeogenesis pathways between LD muscles and the other two groups (BF and TB muscles). There were significant differences in the enrichment degrees of the d-glutamine and d-glutamate metabolic pathways, the alanine, aspartate, and glutamate metabolic pathways between the TB muscles and the other two groups (BF and LD muscles). There is a significant difference in the enrichment degree of the niacin and nicotinamide metabolic pathways between BF and LD muscles. In addition, there were significant differences in the enrichment degree of the histidine metabolism pathway among the three groups of muscles. This study identified key metabolites related to differences in meat quality and flavor formation in different parts of the muscle tissue of Tianzhu white yak through metabolomics analysis, providing a theoretical basis for exploring the molecular regulatory mechanism and molecular breeding of yak meat flavor formation in the future, and also providing a reference for quality trait breeding in other beef cattle.
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•The analysis focused on the flavour and metabolic characteristics of various sections of yak muscle.•The histidine metabolic pathway plays a significant role.•It provides a scientific basis for optimizing the processing and utilization of yak meat.
The methylation level of testicular tissue in young yaks and adult yaks was determined, and the Nsup.6-methyladenosine (msup.6A) level was significantly increased after sexual maturity. Functional ...enrichment analysis of differentially methylated mRNAs screened between the two groups after sequencing showed that they mainly regulated cell development, spermatogenesis, and testicular endocrine function. Functional analysis of the differentially expressed genes screened between the two groups showed that they were involved in the biological processes of mitosis, meiosis, and flagellated sperm motility. Finally, several genes related to spermatogenesis were screened for further verification. Studying the mechanism of spermatogenesis is key to exploring the reproductive characteristics of male yaks. Although Nsup.6-methyladenosine (msup.6A) RNA modification has been reported to regulate spermatogenesis and reproductive function in mammals, the molecular mechanism of msup.6A in yak testis development and spermatogenesis remains largely unknown. Therefore, we collected testicular tissue from juvenile and adult yaks and found that the msup.6A level significantly increased after sexual maturity in yaks. In MeRIP-seq, 1702 hypermethylated peaks and 724 hypomethylated peaks were identified. The hypermethylated differentially methylated RNAs (DMRs) (CIB2, AK1, FOXJ2, PKDREJ, SLC9A3, and TOPAZ1) mainly regulated spermatogenesis. Functional enrichment analysis showed that DMRs were significantly enriched in the adherens junction, gap junction, and Wnt, PI3K, and mTOR signaling pathways, regulating cell development, spermatogenesis, and testicular endocrine function. The functional analysis of differentially expressed genes showed that they were involved in the biological processes of mitosis, meiosis, and flagellated sperm motility during the sexual maturity of yak testis. We also screened the key regulatory factors of testis development and spermatogenesis by combined analysis, which included BRCA1, CREBBP, STAT3, and SMAD4. This study indexed the msup.6A characteristics of yak testicles at different developmental stages, providing basic data for further research of msup.6A modification regulating yak testicular development.
SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of SIM0417 ...plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19.
This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750 mg SIM0417 plus 100 mg ritonavir, 300 mg SIM0417 plus 100 mg ritonavir or placebo every 12 h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676.
Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n = 12), low dose group (n = 12) or placebo (n = 8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of −2.16 ± 0.761 log10 copies/mL (p = 0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR = 3.08, 95% CI 0.968–9.818). SIM0417 plus ritonavir were well tolerated with all adverse events in grade 1.
SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose–response relationship, and the 750 mg SIM0417 plus 100 mg ritonavir was selected as the recommended clinical dose.
The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.
Background: SIM0417 (SSD8432) is an orally administered coronavirus main proteinase (3CLpro) inhibitor with potential anti-SARS-CoV-2 activity. This study aimed to evaluate the efficacy and safety of ...SIM0417 plus ritonavir (a pharmacokinetic enhancer) in adults with COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, phase 1b study in China. Adults with asymptomatic infection, mild or moderate COVID-19 were randomly assigned (3:3:2) to receive either 750 mg SIM0417 plus 100 mg ritonavir, 300 mg SIM0417 plus 100 mg ritonavir or placebo every 12 h for 10 doses. The main efficacy endpoints included SARS-CoV-2 viral load, proportion of participants with positive SARS-CoV-2 nucleic acid test and time to alleviation of COVID-19 symptoms. This trial is registered with ClinicalTrials.gov, NCT05369676. Findings: Between May 12 and August 29, 2022, 32 participants were enrolled and randomised to high dose group (n = 12), low dose group (n = 12) or placebo (n = 8). The viral load change from baseline in high dose group was statistically lower compared with placebo, with a maximum mean difference of −2.16 ± 0.761 log10 copies/mL (p = 0.0124) on Day 4. The proportion of positive SARS-CoV-2 in both active groups were lower than the placebo. The median time to sustained alleviation of COVID-19 symptoms was 2.0 days in high dose group versus 6.0 days in the placebo group (HR = 3.08, 95% CI 0.968–9.818). SIM0417 plus ritonavir were well tolerated with all adverse events in grade 1. Interpretation: SIM0417 plus ritonavir was generally well tolerated. The efficacy of SIM0417 showed a monotonic dose–response relationship, and the 750 mg SIM0417 plus 100 mg ritonavir was selected as the recommended clinical dose. Funding: The study was funded by Jiangsu Simcere Pharmaceutical Co., Ltd.
