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Gallbladder neuroendocrine carcinomas (GB-NECs) are a rare subtype of malignant gallbladder cancer (GBC). The genetic and molecular characteristics of GB-NECs are rarely reported. This study aims to assess the frequency of microsatellite instability (MSI) in GB-NECs and characterize their clinicopathologic and molecular features in comparison with gallbladder adenocarcinomas (GB-ADCs). Data from six patients with primary GB-NECs and 13 with GB-ADCs were collected and reevaluated. MSI assay, immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2), comprehensive genomic profiling (CGP) via next-generation sequencing (NGS), and evaluation of tumor mutation burden (TMB) were conducted on these samples. The six GB-NEC cases were all female, with a mean age of 62.0±9.2 years. Of these, two cases were diagnosed as large cell neuroendocrine carcinomas (LCNECs), while the remaining four were small cell neuroendocrine carcinomas (SCNECs). Microsatellite states observed in both GB-NECs and GB-ADCs were consistently microsatellite stable (MSS). Notably, TP53 (100%, 6/6) and RB1 (100%, 6/6) exhibited the highest mutation frequency in GB-NECs, followed by SMAD4 (50%, 3/6), GNAS (50%, 3/6), and RICTOR (33%, 2/6), with RB1, GNAS, and RICTOR specifically present in GB-NECs. Immunohistochemical (IHC) assays of p53 and Rb in the six GB-NECs were highly consistent with genetic mutations detected by targeted NGS. Moreover, no statistical difference was observed in TMB between GB-NECs and GB-ADCs (P=0.864). Although overall survival in GB-NEC patients tended to be worse than in GB-ADC patients, this difference did not reach statistical significance (P=0.119). This study has identified the microsatellite states and molecular mutation features of GB-NECs, suggesting that co-mutations in TP53 and RB1 may signify a neuroendocrine inclination in GB-NECs. The IHC assay provides an effective complement to targeted NGS for determining the functional status of p53 and Rb in clinical practice.
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Objectives: Dihydroartemisinin (DHA), an artemisinin derivative extracted from the traditional Chinese medicinal herb Artemisia annua, has the potential to suppress head and neck squamous cell carcinoma (HNSCC) progression. However, the mechanisms underlying these effects remain unclear. Therefore, we aimed to examine the mechanisms underlying the effects of DHA on tumor invasion and migration. Methods: Human HNSCC cell lines CAL-27 and FaDu were exposed to varying DHA concentrations (0, 5, 20, and 80 µM) for 24 h. Cell proliferation, invasion, and migration were assessed using CCK8, transwell, and wound-healing assays, respectively. Quantitative real-time PCR, western blotting, and immunofluorescence were used to assess the expression levels of the target genes and proteins. Results: DHA suppressed the invasion and migration of CAL-27 and FaDu cells. Additionally, miR-195-5p suppressed the invasion and migration of HNSCC cells. This study revealed significant differences in the expression of miR-195-5p and TENM2 between clinical samples and multiple public databases. DHA treatment and miR-195-5p overexpression significantly reduced TENM2 expression in HNSCC cells, which suggested that miR-195-5p overexpression enhanced the inhibitory effect of DHA on TENM2. Conclusions: This study provides the first evidence that DHA inhibits cell invasion and migration by regulating the miR-195-5p/TENM2 axis in HNSCC cells, suggesting it as a potentially effective treatment strategy for HNSCC.
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Globally, influenza poses a substantial threat to public health, serving as a major contributor to both morbidity and mortality. The current vaccines for seasonal influenza are not optimal. A novel recombinant hemagglutinin (rHA) protein-based quadrivalent seasonal influenza vaccine, SCVC101, has been developed. SCVC101-S contains standard dose protein (15µg of rHA per virus strain) and an oil-in-water adjuvant, CD-A, which enhances the immunogenicity and cross-protection of the vaccine. Preclinical studies in mice, rats, and rhesus macaques demonstrate that SCVC101-S induces robust humoral and cellular immune responses, surpassing those induced by commercially available vaccines. Notably, a single injection with SCVC101-S can induce a strong immune response in macaques, suggesting the potential for a standard-dose vaccination with a recombinant protein influenza vaccine. Furthermore, SCVC101-S induces cross-protection immune responses against heterologous viral strains, indicating broader protection than current vaccines. In conclusion, SCVC101-S has demonstrated safety and efficacy in preclinical settings and warrants further investigation in human clinical trials. Its potential as a valuable addition to the vaccines against seasonal influenza, particularly for the elderly population, is promising.
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Atomic clocks with higher frequency stability and accuracy than traditional space-borne atomic clocks are the cornerstone of long-term autonomous operation of space-time-frequency systems. We proposed a space cold atoms clock based on an intracavity cooling scheme, which captures cold atoms at the center of a microwave cavity and then executes in situ interactions between the cold atoms and microwaves. As a result of the microgravity environment in space, the cold atoms can interact with the microwaves for a longer time, which aids in realizing a high-precision atomic clock in space. This paper presents the overall design, operational characteristics, and reliability test results of the space atomic clock based on the intracavity cooling scheme designed for the operation onboard the China space station. In addition, the engineering prototype performance of the space cold atoms microwave clock is also presented. The ground test results for the clock show a fractional frequency stability of 1.1 × 10-12 τ-1/2 reaching 2.5 × 10-15 at 200,000 s, providing solid technical and data support for its future operation in orbit.
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The IEEE 802.11ah standard is introduced to address the growing scale of internet of things (IoT) applications. To reduce contention and enhance energy efficiency in the system, the restricted access window (RAW) mechanism is introduced in the medium access control (MAC) layer to manage the significant number of stations accessing the network. However, to achieve optimized network performance, it is necessary to appropriately determine the RAW parameters, including the number of RAW groups, the number of slots in each RAW, and the duration of each slot. In this paper, we optimize the configuration of RAW parameters in the uplink IEEE 802.11ah-based IoT network. To improve network throughput, we analyze and establish a RAW parameters optimization problem. To effectively cope with the complex and dynamic network conditions, we propose a deep reinforcement learning (DRL) approach to determine the preferable RAW parameters to optimize network throughput. To enhance learning efficiency and stability, we employ the proximal policy optimization (PPO) algorithm. We construct network environments with periodic and random traffic in an NS-3 simulator to validate the performance of the proposed PPO-based RAW parameters optimization algorithm. The simulation results reveal that using the PPO-based DRL algorithm, optimized RAW parameters can be obtained under different network conditions, and network throughput can be improved significantly.
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Host-microbiome interplay from birth is essential for immune imprinting and tuning. Live gut microbes and microbial-derived metabolites regulate the development and modulation of the immune system, but whether microbial metabolites solely are sufficient to induce immune maturation remains unclear. Sterile faecal filtrates (FFT) were generated from murine gut contents. Newborn germ-free (GF) mice were treated twice daily with FFT (GF-FFT) or saline (GF-NaCl) from post-natal day 5 until 4 weeks of age. A third group of GF neonates were conventionalized by the transfer of caecal microbiota with live gut microbes. Host immune compartments were comprehensively immunophenotyped and systemically analysed in all available immune-related organs using flow cytometry. Oral FFT was associated with reduced survival among neonates (n = 7/19; 36.8% mortality), while saline treatment was well tolerated (n = 1/17, 5.9% mortality). Four-week-old FFT-treated pups were comparable in body weight to GF-NaCl, and the major B-cell, conventional T-cell and unconventional T-cell subsets were unchanged from saline-treated mice. Live bacteria administered during early life induced clear changes in proportions of B cells, T cells and T-cell subsets in all mucosal tissues and secondary lymphoid organs compared to GF-FFT, including restoration of intestinal natural killer T (NKT) cells with characteristics similar to conventional pups. Our findings show that oral administration of a FFT made of microbial metabolites, antigens and bacteriophages alone is insufficient to induce normal immune development elicited by the presence of live bacteria. Reduced survival during neonatal FFT treatment suggests a potential bioactive attribute of sterile faecal filtrates.
Subject(s)
B-Lymphocytes , Sodium Chloride , Animals , Mice , Administration, Oral , Bacteria , FecesABSTRACT
Noncoding RNAs, including miRNAs (microRNAs) and circRNAs (circular RNA), are crucial regulators of myoblast proliferation and differentiation during muscle development. However, the specific roles and molecular mechanisms of circRNAs in muscle development remain poorly understood. Based on the existing circRNA-miRNA-mRNA network, our study focuses on circUBE3C, exploring its differential expression in fetal and adult muscle tissue of the cattle and investigating its impact on myoblast proliferation, apoptosis, and differentiation. The functional analysis of overexpression plasmids and siRNAs (small interfering RNAs) targeting circUBE3C was comprehensively evaluated by employing an array of advanced assays, encompassing CCK-8 (cell counting kit-8), EdU (5-ethynyl-20-deoxyuridine), flow cytometry, western blot analysis, and RT-qPCR. In vivo investigations indicated that overexpression of circUBE3C impedes the process of skeletal muscle regeneration. Mechanistically, we demonstrated that circUBE3C interacts with miR-191 and alleviates the suppression of p27 through cytoplasmic separation, bioinformatics prediction, dual-luciferase reporter assay, and RIP (RNA immunoprecipitation). Our findings indicate that the novel circRNA circUBE3C competitively binds to miR-191, thereby inhibiting proliferation and promoting apoptosis in bovine primary myoblasts and unveiling a regulatory pathway in bovine skeletal muscle development. These findings expand our understanding of circRNA functions in mammals and provide a basis for further exploration of their role in myogenesis and muscle diseases.
Subject(s)
MicroRNAs , RNA, Circular , Animals , Cattle , Cell Differentiation/genetics , Cell Proliferation/genetics , Mammals/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Muscle Development/genetics , Myoblasts/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Small Interfering/metabolism , Cells, Cultured , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
BACKGROUND & AIMS: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms. METHODS: Biopsy specimens of explanted livers and endoscopy-guided sampling were used to assess the CD100 expression by spatial transcriptomics, immune imaging, and high-dimensional flow cytometry. To model pathogenic cholangiocyte-immune cell interaction, splenocytes from mutation-specific mice were cocultured with cholangiocytes. Pathogenic pathways were pinpointed by RNA sequencing analysis of cocultured cells and cross-validated in patient materials. RESULTS: CD100 is mainly expressed by immune cells in the liver and shows a unique pattern around PSC bile ducts with RNA-level colocalization but poor detection at the protein level. This appears to be due to CD100 cleavage as soluble CD100 is increased. Immunophenotyping suggests biliary-infiltrating T cells as the major source of soluble CD100, which is further supported by reduced surface CD100 on T cells and increased metalloproteinases in cholangiocytes after coculturing. Pathogenic T cells that adhered to cholangiocytes up-regulated genes in the T-helper 17 cell differentiation pathway, and the CD100 mutation boosted this process. Consistently, T-helper 17 cells dominate biliary-resident CD4 T cells in patients. CONCLUSIONS: CD100 exerts its functional impact through cholangiocyte-immune cell cross talk and underscores an active, proinflammatory role of cholangiocytes that can be relevant to novel treatment approaches.
Subject(s)
Biliary Tract , Cholangitis, Sclerosing , Cholangitis , Humans , Animals , Mice , Liver/pathology , Bile Ducts/pathology , Biliary Tract/pathology , Epithelial Cells/pathology , Cell Differentiation , Cholangitis, Sclerosing/pathologyABSTRACT
OBJECTIVES: The early life microbiome has been linked to inflammatory diseases in adulthood and a role for the microbiome in bile duct inflammation is supported by both human and murine studies. We utilized the NOD.c3c4 mouse model that develops a spontaneous immune-driven biliary disease with a known contribution of the microbiome to evaluate the temporal effects of the early life microbiome. MATERIALS AND METHODS: Germ-free (GF) NOD.c3c4 mice were conventionalized into a specific pathogen free environment at birth (conventionally raised, CONV-R) or at weaning (germ-free raised, GF-R) and compared with age and gender-matched GF and conventional (CONV) NOD.c3c4 mice. At 9 weeks of age, liver pathology was assessed by conventional histology and flow cytometry immunophenotyping. RESULTS: Neonatal exposure to microbes (CONV-R) increased biliary inflammation to similar levels as regular conventional NOD.c3c4 mice, while delayed exposure to microbes (GF-R) restrained the biliary inflammation. Neutrophil infiltration was increased in all conventionalized mice compared to GF. An immunophenotype in the liver similar to CONV was restored in both CONV-R and GF-R compared to GF mice displaying a proportional increase of B cells and reduction of T cells in the liver. CONCLUSIONS: Microbial exposure during early life has a temporal impact on biliary tract inflammation in the NOD.c3c4 mouse model suggesting that age-sensitive interaction with commensal microbes have long-lasting effects on biliary immunity that can be of importance for human cholangiopathies.
Subject(s)
Cholangitis , Mice , Humans , Animals , Mice, Inbred NOD , Liver/pathology , Inflammation/pathology , Disease Models, Animal , Bile Ducts/pathologyABSTRACT
In the conservation of livestock and poultry resources, population genetic diversity and genetic structure of the conservation population are important factors affecting the effectiveness of conservation. In this study, whole-genome resequencing technology was used to detect genomic variation in 100 Qinchuan cattle (30 bulls and 70 cows). By analyzing population genetic diversity, runs of homozygosity (ROH) distribution features, kinship relationships, and family structure, the conservation effectiveness of Qinchuan cattle was comprehensively evaluated. The results showed that a total of 20,968,017 high-quality SNPs were detected in 100 Qinchuan cattle, the average minimum allele frequency was 0.191±0.124, the average polymorphic information content was 0.279±0.131, and the average observed heterozygosity was 0.275±0.131, the average expected heterozygosity is 0.279±0.131, indicating that the genetic diversity of the Qinchuan cattle conservation population is relatively rich. The average identity by state (IBS) distance of the Qinchuan conservation population was 0.243±0.020, with a value of 0.242±0.021 for the bulls. The results of the kinship G-matrix were consistent with the results of the IBS distance matrix, both showing that some individuals in the conservation population had close kinship. A total of 8258 genomic ROH were detected in 100 Qinchuan cattle, with a total length of 9.64 GB. The average length of ROH fragments was 1.167±1.203 Mb, 69.35% of the ROH were short ROH with a length of 0.5~1 Mb, and the average total length of ROH per individual was 96.40 Mb. The average inbreeding coefficient based on ROH was 0.039±0.039, with a value of 0.044±0.035 for the bulls, indicating that some bulls had a certain degree of inbreeding accumulation. The results of the phylogenetic tree combined with kinship analysis showed that the individuals in the Qinchuan cattle conservation population could be divided into eight families, including seven families with bulls and one family without bulls. This study demonstrated that the genetic diversity of the Qinchuan conservation population is relatively rich, with no significant inbreeding accumulation, but there is a risk of inbreeding among some individuals. Therefore, it is necessary to strengthen selection and mating to ensure the sustainable development of Qinchuan cattle resources.
Subject(s)
Cattle , Inbreeding , Animals , Cattle/genetics , Female , Male , Genome/genetics , Genotype , Homozygote , Phylogeny , Polymorphism, Single NucleotideABSTRACT
SCOPE: Inflammatory responses reduce milk production in lactating sow. Silymarin (Silibinin is main component) reduces the inflammatory reaction and increases milk yield in lactating sow in the previous study. In the present study, silibinin may be a previously unrecognized nutrients in inflammatory resolution in porcine mammary epithelial cells (PMECs) is hypothesized. METHODS AND RESULTS: PMECs are treated with or without lipopolysaccharide (LPS) in the absence or presence of silibinin to test cell viability, cell cycle, cell apoptosis, cellular inflammatory factors, and signaling protein phosphorylation and expression. Silibinin promotes the proliferation of PMEC independent of the estrogen pathway. In LPS-induced damage of PMECs, silibinin protects cell proliferation, as well as reduced cell apoptosis. Silibinin reverses the LPS-induced increase in tumor necrosis factor-alpha (TNF-α) expression compared with control. In addition, silibinin accentuates the LPS-induced decrease in the key proteins phosphorylated-ribosomal protein S6 (p-S6) and phosphorylated-mammalian target of rapamycin (p-mTOR) of the mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, silibinin reverses the increase in phosphorylated-nuclear factor-kappa B p65 (p-NF-κB p65), phosphorylated-Ikappab-alpha (p-IκB-α), and phosphorylated-Mitogen-activated protein kinase p38 (p-MAPK p38) expression in LPS-induced damage in PMECs. CONCLUSION: This study highlights silibinin-mTOR/NF-κB axis plays an important role in the control of inflammation in PMECs, and suggests that silibinin may be an effective dietary strategy to alleviate the inflammatory response in lactating sow.
Subject(s)
Lipopolysaccharides , NF-kappa B , Female , Animals , Swine , NF-kappa B/metabolism , Lipopolysaccharides/toxicity , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/pharmacology , Silybin/adverse effects , Lactation , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Tumor Necrosis Factor-alpha/metabolism , Epithelial Cells/metabolism , Mammals/metabolismABSTRACT
Introduction: Despite of growing evidence linking silica nanoparticles (SiNPs), one of the global-top-three-produced and -used nanoparticle (NP), to human health risks, there remain many knowledge gaps over the adverse effects of SiNPs exposure on cardiovascular system and the underlying molecular mechanisms. Methods: In this study, the ferroptotic effects of SiNPs (20 nm; 0, 25, 50, and 100 µg/mL) on human umbilical vein endothelial cells (HUVECs) and the possible molecular mechanism were studied with the corresponding biochemical and molecular biology assays. Results and discussion: The results showed that at the tested concentrations, SiNPs could decrease HUVEC viability, but the deferoxamine mesylate (an iron ion chelator) might rescue this reduction of cell viability. Also, increased levels of intracellular reactive oxygen species and enhanced mRNA expression of lipid oxidation enzymes (ACSL4 and LPCAT3) with increase in lipid peroxidation (malondialdehyde), but decreased ratios of intracellular GSH/total-GSH and mitochondrial membrane potential as well as reduced enzymatic activities of anti-oxidative enzymes (CAT, SOD, and GSH-PX), were found in the SiNPs-treated HUVECs. Meanwhile, increase in p38 protein phosphorylation and decrease in NrF2 protein phosphorylation with reduced mRNA expressions of downstream anti-oxidative enzyme genes (CAT, SOD1, GSH-PX, and GPX4) was identified in the SiNPs-exposed HUVECs. These data indicated that SiNPs exposure might induce ferroptosis in HUVECs via p38 inhibiting NrF2 pathway. Ferroptosis of HUVECs will become a useful biomarker for assessing the cardiovascular health risks of environmental contaminants.
Subject(s)
Ferroptosis , Nanoparticles , Humans , Human Umbilical Vein Endothelial Cells/metabolism , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/metabolism , Silicon Dioxide/pharmacology , Nanoparticles/chemistry , RNA, Messenger/metabolism , RNA, Messenger/pharmacologyABSTRACT
VISFATIN is an adipose cytokine that has been proved to correlate with growth and development traits. In a previous study from our lab, two insertion/deletions (indels; including a 35-bp insertion at its intron 4 and a 6-bp deletion in intron 5) were identified within the VISFATIN gene. To validate these indels and evaluate their association with growth traits in Chinese cattle, a total of 413 samples from four Chinese indigenous breeds and 217 samples from Chinese breeds were detected. Three genotypes (WW, WI and II) at intron 4 were detected based on the 35-bp insertion (allele I) or deletion (allele W) and showed moderate polymorphism in all samples. Two genotypes (WW and WD) at intron 5 were detected based on the 6-bp deletion (allele D) or insertion (allele W) in Xianan (XN) cattle and Jinnan (JN) cattle population but showed poor polymorphisms. Association analysis illustrated that the indel at intron 4 is significantly associated with chest girth, rump length and body weight in Ji'an (JA) cattle and the indel at intron 5 can cause a significant difference in rump length in JN cattle. To our knowledge, it is the first time it has been shown that indels within the VISFATIN gene are associated with growth traits in the two Chinese indigenous cattle breeds. These findings suggest that the VISFATIN gene can be used as a molecular marker for JN and JA cattle breeding.
Subject(s)
Nicotinamide Phosphoribosyltransferase , Polymorphism, Genetic , Cattle/genetics , Animals , Nicotinamide Phosphoribosyltransferase/genetics , Phenotype , Genotype , Body Weight/geneticsABSTRACT
FOXO1 (FKHR) gene, as a transcription factor, plays a vital role in animal growth and development, participating in many biological processes. The aim of this study was to ascertain Insertion/deletions (Indels) polymorphism within bovine FoxO1 gene in 679 Chinese adult cows and associate them with stature traits. Two Indels (named as Indel-3 and Indel-4, recorded as rs383545622 and rs525318770 in NCBI, respectively) were successfully genotyped by the Once PCR method, which was reliable, rapid and cost effective for simultaneous detection of two or more Indels. Indel-3 and Indel-4 were located at the second intron. All four different haplotypes (H1: D3D4, H2: I3D4, H3: D3I4, H4: I3I4) could be identified, and the D (del-) allele, DD (del-/del-) genotype and D3D4 haplotype retained the highest frequency. However, individuals with DI (D3I3, D4I4 or H1H4/H2H3 genotype) showed significantly better phenotypic traits than those with the other genotypes in Nanyang cattle, showing a hybrid vigor. The results implied that this DI genotype can be applied to early selective breeding to improve the productivity of Nanyang cattle. Our results suggested that these two Indels within the bovine FoxO1 gene might be used as genetic markers for marker-assisted selection (MAS) in cattle breeding and genetics.
Subject(s)
Biological Phenomena , Forkhead Box Protein O1 , Polymorphism, Genetic , Animals , Cattle/genetics , Female , Breeding , Genotype , Haplotypes/genetics , Phenotype , Polymorphism, Single Nucleotide , Forkhead Box Protein O1/geneticsABSTRACT
Agarwood (Aquilaria sinensis) is one of the most important resin-containing plants used to produce agar around the world and it is a precious herbal medicine usually combined with other herbs. In this study, we used the Illumina sequencing technique to explore the agarwood bacterial community structure from four different incense formations of agarwood, including healthy agarwood, drilling agarwood, liquid fermentation agarwood, and insect attack agarwood. Our results showed that 20 samples of three different incense-formation methods of agarwood and healthy agarwood acquired 1,792,706 high-quality sequences. In-depth investigation showed that when the diversity of agarwood bacterial species was higher, the agarwood incense quality was higher as well. Among healthy agarwood, drilling agarwood, fermentation agarwood, and insect attack agarwood, the bacterial community structure had significant changes. Natural agarwood, such as insect attack agarwood, kept more bacterial community structure, and the incense quality was better. Furthermore, we observed that in the healthy agarwood, Amnibacterium and Delftia were the predominant bacteria. Actinoplanes, Bordetella, and Sphingobacterium were the dominant bacteria in the drilling agarwood. Additionally, Pelagibacterium and Methylovirgula were some of the main bacteria in the fermentation liquid agarwood and the insect attack agarwood, while Cellulomonas and Aeromicrobium were the dominant bacteria. This research provides a basis for further research into the underlying mechanisms of incense production, as well as the bacterial community applications of agarwood production.
ABSTRACT
Inflammatory responses reduce milk production in lactating sows. Silymarin may modulate inflammatory reactions. Here, we aimed to verify whether dietary silymarin supplementation could alleviate inflammatory responses in lactating sows through microbiota change in the gut. We also investigated how silymarin impacts inflammatory response in lactating sows. One hundred and ten sows were randomly assigned to a control diet (basal diet) or treatment diet (basal diet and 40 g/d silymarin) from the 108th day of gestation to weaning. Blood, milk, and feces from sows were collected for analysis. It was shown in the results that dietary silymarin supplementation decreased the level of pro-inflammatory cytokine IL-1ß (p < 0.05) on the 18th day of lactation in the blood of the sows. Dietary silymarin supplementation tended to decrease (p = 0.06) somatic cell count in the colostrum of sows. Dietary silymarin supplementation reduced the gut bacterial community and the richness of the gut microbial community (p < 0.01) using 16S rRNA gene sequencing. The fecal microbes varied at different taxonomic levels in the lactating sows with silymarin supplementation. The most representative changes included an increase in the relative abundance of Fibrobacteres and Actinobacteria (p < 0.05) and tended to reduce the relative abundance of Spirochaetaes and Tenericutes (p = 0.09, 0.06) at the phylum level. It is suggested that dietary silymarin supplementation in late gestation until lactation has anti-inflammatory effects in lactation sow, which could be associated with the modulation of gut microbiota.
ABSTRACT
This paper adopts the algorithm of the deep neural network to conduct in-depth research and analysis on the factors associated with the improvement of English translation ability. This study focuses on text complexity, adding discourse complexity features in addition to focusing on lexical and syntactic dimensions, exploring the application of neural network algorithm in the construction of text complexity grading model based on feature optimization, and examining the performance and generalization ability of the model. The rationality of the grading of the material is verified. After determining the model input features and training corpus, different classification algorithms were used to build the models and compare their performance. Meanwhile, compared with the models constructed based on common traditional readability formulas and other single-dimensional features, the models constructed based on the feature set of this study have significant advantages, with 20 to 30 percentage points higher in each performance evaluation index. The pseudo-parallel corpus is constructed, back translation is performed after obtaining the pseudo-parallel corpus, and finally, the data migration effect is measured and recorded on the low-resource Chinese-English parallel corpus and Tibetan-Chinese parallel corpus, and the cycle continues until the model performance is no longer improved. The low-resource neural machine translation model based on model migration learning improved 3.97 and 2.64 BLEU values in the low-resource English translation task, respectively, and reduced the training time; based on this, the data migration learning method further improved 2.26 and 2.52 BLEU values.
Subject(s)
Algorithms , Neural Networks, Computer , Asian People , Comprehension , Humans , TranslationsABSTRACT
ASB-3 is one of the 18 members of ASB gene family. As a special negative regulation factor of TNF-R2, ASB-3 inhibits the signal transduction of JNK-TNF-R2 and JNK-STAT signaling pathway by TNF-R2 protein. In this study, the genetic polymorphisms of ASB-3 were detected in total of 637 from Qinchuan, Jinnan and Xianan cattle using the sequence of mixed DNA pool, Tetra-primer ARMS-PCR and PCR-RFLP methods. Four mutation sites were detected including the g.C41255T, g.G74754A, and g.T75438C were synonymous mutation, whereas the g.C115213T was missense mutation (Pro > Ser). The associated analysis of four polymorphic loci of ASB-3 gene respectively with growth traits in the three cattle breeds. The result showed that SNP1 site was significantly related with Qinchuan cattle height and TT was the dominant genotype; SNP2 had a significant relationship with body length of Xianan cattle and cross department height of Qinchuan cattle, AA was the dominant genotype; SNP3 was significantly related to cross height of Xianan cattle, TT was the dominant genotype; SNP4 site was significantly correlated with body height of Xianan cattle and cross height of Jinnan cattle. Genotype combinations were only significantly correlated with the hucklebone width in the adult Qinchuan cattle. The combination genotype CTAGCTCC was outperformed other combination genotypes of Qinchuan cattle. The results showed that ASB-3 could be an important candidate gene and the four SNPs in ASB-3 can be used for molecular marker-assisted selection of four beef cattle breeds.
Subject(s)
Polymorphism, Single Nucleotide , Receptors, Tumor Necrosis Factor, Type II , Animals , Cattle/genetics , China , Genetic Association Studies , Genotype , Phenotype , Receptors, Tumor Necrosis Factor, Type II/geneticsABSTRACT
Spike-layer uniformity (SLU), the consistency of the spike distribution in the vertical space, is an important trait. It directly affects the yield potential and appearance. Revealing the genetic basis of SLU will provide new insights into wheat improvement. To map the SLU-related quantitative trait loci (QTL), 300 recombinant inbred lines (RILs) that were derived from a cross between H461 and Chinese Spring were used in this study. The RILs and parents were tested in fields from two continuous years from two different pilots. Phenotypic analysis showed that H461 was more consistent in the vertical spatial distribution of the spike layer than in Chinese Spring. Based on inclusive composite interval mapping, four QTL were identified for SLU. There were two major QTL on chromosomes 2BL and 2DL and two minor QTL on chromosomes 1BS and 2BL that were identified. The additive effects of QSlu.sicau-1B, Qslu.sicau-2B-2, and QSlu.sicau-2D were all from the parent, H461. The major QTL, QSlu.sicau-2B-2 and QSlu.sicau-2D, were detected in each of the conducted trials. Based on the best linear unbiased prediction values, the two loci explained 23.97% and 15.98% of the phenotypic variation, respectively. Compared with previous studies, the two major loci were potentially novel and the two minor loci were overlapped. Based on the kompetitive allele-specific PCR (KASP) marker, the genetic effects for QSlu.sicau-2B-2 were validated in an additional RIL population. The genetic effects ranged from 26.65% to 32.56%, with an average value of 30.40%. In addition, QSlu.sicau-2B-2 showed a significant (p < 0.01) and positive influence on the spike length, spikelet number, and thousand kernel weight. The identified QTL and the developed KASP marker will be helpful for fine-mapping these loci, finally contributing to wheat breeding programs in a marker-assisted selection way.
Subject(s)
Quantitative Trait Loci , Triticum , Chromosome Mapping , Phenotype , Plant Breeding , Polymorphism, Single Nucleotide , Triticum/geneticsABSTRACT
Primary sclerosing cholangitis (PSC) is associated with altered microbiota of the gut and bile. Mucosal-associated invariant T (MAIT) cells, enriched in human liver, uniquely recognize microbial-derived metabolites. This study aimed to determine whether bile from patients with PSC contains antigens activating MAIT cells. Bile was collected at the time of liver transplantation from patients with PSC (n = 28). The bile samples were either directly incubated with peripheral blood mononuclear cells from healthy donors or with antigen-presenting cells followed by co-culture with peripheral blood mononuclear cells. MAIT cell activation was assessed by flow cytometry. An anti-MR1 antibody was used to determine whether the activation was major histocompatibility complex class I-related protein (MR1) restricted. Biliary microbiota profiles were generated using 16S rRNA amplicon sequencing, and the abundance of the bacterial gene ribD was predicted. Eight of 28 bile samples could activate MAIT cells. This activation was partly MR1-dependent in five of eight bile samples. Microbial DNA was detected in 15 of 28 bile samples, including the five bile samples leading to MR1-dependent activation. A higher abundance of the ribD gene expression in the group of bile samples that could activate MAIT cells was predicted on the basis of the 16S sequencing. In co-culture experiments, cholangiocytes could take up and present biliary antigens to MAIT cells. These findings suggest a pathophysiological pathway in PSC connecting the immune system and the microbiome.