Moorelaugesen4318

In this study, the complete proteome of goat ejaculated semen including spermatozoa and seminal plasma was established, applying a tandem mass tag (TMT) labeling together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In seminal plasma, 2299 proteins were identified and 2098 proteins were quantified. The GO analysis demonstrated that 32% proteins were involved in metabolic activities. 46% proteins are located at intracellular region, intracellular organelle, and membrane-bounded organelle. Regarding molecular function, 40% proteins are engaged on protein binding, hydrolase activity, and ion binding. The KEGG analysis indicated a primary involvement of the identified proteins in protein processing in endoplasmic reticulum, lysosome, and proteome. In spermatozoa, 2491 proteins were identified and quantified. 39% proteins are involved in metabolic activities. 48% proteins are located at intracellular region, intracellular organelle, and membrane-bounded organelle. 38% proteins are engaged on protein binding, hydrolase activity, and ion binding. The KEGG analysis demonstrated their roles derived from the identified proteins in proteasome, glycolysis, pyruvate metabolism, and citrate cycle. Additionally, 1312 proteins were simultaneously presented in spermatozoa and seminal plasma. The involvement of 42% proteins in metabolic activities were observed. 47% proteins are located at intracellular region, intracellular organelle, and membrane-bounded organelle. The common proteins are mainly engaged on protein processing in endoplasmic reticulum, proteome, glycolysis, lysosome, and citrate cycle. Collectively, this study established the protein database of goat semen. More studies should be used to elucidate functionality of these identified proteins.The aim of this research was to analyze and model the aptitude of temperate areas to support permanent populations of the cattle tick Rhipicephalus microplus, which is principally distributed in tropical and subtropical areas. This work integrated field-derived data of tick development with temperature and land-based models of tick spread in Argentina. The integrated analysis of the results suggest that approximately 31°S is the southern limit where R. microplus finds appropriate climatic conditions to be established permanently. The establishment of permanent populations of R. microplus south of this latitudinal threshold is currently restricted because the low temperatures in autumn and winter inhibit the development of its eggs, but the introduction of cattle infested with R. microplus from early spring to late summer in temperate areas could produce engorged females laying eggs that would originate viable larvae from late spring to winter. The comparison of the temperature-based maps of habitat suitability with those obtained considering the lands suitable for livestock grazing, clearly shows that the models based only on climatic variables overestimate the potential dispersal of the cattle tick. The outcomes of this study suggest that an increase of temperature in the months of autumn and winter around 2°-2.75 °C should be necessary for the establishment of permanent populations of R. micoplus in the region belonging to temperate areas. This would allow that a tick generation emerged in early spring due to the overwintering of eggs and larvae originated from females detached from cattle during autumn or early winter.Avian pathogenic Escherichia coli (APEC) is one of the most common avian bacterial diseases globally. The bone marrow is a reservoir of immature immune cells. To elucidate the role of bone marrow microRNAs (miRNAs) in regulating the host response to APEC infection, we performed miRNA-seq to investigate alterations in the expression of bone marrow miRNAs in three groups of specific pathogen-free chickens non-challenged (NC) and challenged with APEC for 12 h (C12) and 24 h (C24). Twenty and 19 differentially expressed miRNAs (fold change >2, P less then 0.01) were identified on comparing the NC and C12 and the NC and C24 groups, respectively. On functional annotation analysis of target genes of differentially expressed miRNAs, we found that the gene ontology term "immune system process" was significantly enriched at both 12 h and 24 h; moreover, several important signaling pathways were triggered in response to APEC infection, such as MAPK, cGMP-PKG, Notch, and cAMP pathways. In addition, we performed reverse transcription quantitative real-time PCR (qRT-PCR) to validate the differential expression of miRNAs. qRT-PCR data were similar to the sequencing data. On constructing an miRNA-target gene network, gga-miR-2127, gga-miR-6643-5p, and gga-miR-6567-3p were found to potentially play a vital role in the immune process. Overall, our findings provide deeper insights into miRNA transcriptome changes involved in the immune response of the chicken bone marrow to APEC infection.Oral antibiotics can influence cancers and immunotherapy by interfering with the intestinal microbiota. However, the association between oral antibiotics and oral squamous cell carcinoma (OSCC) as well as the mechanisms underlying the effects of oral antibiotics on OSCC remain unclear. Here, we found that oral antibiotics cocktail (4Abx) promoted the tumor development and shifted the microbiota, decreasing the abundance of probiotic bacteria, and altered microbial metabolism in the gut of OSCC mice, increasing tyrosine and decreasing glutamate levels. In vitro experiments showed that tyrosine upregulated the PD-1 expression in T cells, SCC7 cell proliferation, and necroptosis expression. IL-10 expression level in CD11c+ cells was reduced by glutamate. Furthermore, the expression of the necroptosis-related proteins, including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL), was higher in the OSCC mice treated with 4Abx. Supplementation with glutamate or healthy mouse feces by gavage alleviated the tumor-promoting effect of 4Abx with restored balance of microbial metabolism. Overall, we identified the detrimental role of oral antibiotics in promoting OSCC development through altered intestinal microbiota, microbial metabolism, and immune dysbiosis, implying the need for antibiotic stewardship in OSCC treatment.

In this pre-clinical study, we designed a candidate vaccine based on severe acute respiratory syndrome-related -coronavirus 2 (SARS-CoV-2) antigens and evaluated its safety and immunogenicity.

SARS-CoV-2 recombinant protein antigens, including truncated spike protein (SS1, lacking the N-terminal domain of S1), receptor-binding domain (RBD), and nucleoprotein (N) were used. Immunization program was performed via injection of RBD, SS1+RBD, and SS1+N along with different adjuvants, Alum, AS03, and Montanide at doses of 0, 40, 80, and 120μg at three-time points in mice, rabbits, and primates. The humoral and cellular immunity were analyzed by ELISA, VNT, splenocyte cytokine assay, and flow cytometry.

The candidate vaccine produced strong IgG antibody titers at doses of 80 and 120μg on days 35 and 42. Even though AS03 and Montanide produced high-titer antibodies compared to Alum adjuvant, these sera did not neutralize the virus. Strong virus neutralization was recorded during immunization with SS1+RBD and RBD with Alum. AS03 and Montanide showed a strong humoral and cellular immunity; however, Alum showed mild to moderate cellular responses. Ultimately, no cytotoxicity and pathologic change were observed.

These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.

These findings strongly suggest that RBD with Alum adjuvant is highly immunogenic as a potential vaccine.

Zedoray oil (ZO) is the main component of Curcuma zedoaria, one traditional herb used for dispersing stasis clinically in China. Previously, the potential of ZO was discovered against lethal and acute liver injury (ALI) mice with little impact on the immune, which deserved further study.

An approach combined systems pharmacology with GC-MS metabolomics was applied for predicting pathways affected by ZO. Muvalaplin Subsequently, H

O

and tertbutyl hydroperoxide (t-BHP) were respectively applied to induce the ALI model in vitro for validation.

First, systems pharmacology and intracellular metabolites suggested that ZO might regulate oxidative stress via PI3K/Akt/FoxO1 pathway, TCA cycle, pantothenate, and CoA biosynthesis, beta-alanine metabolism, and propanoate metabolism. Further, levels of ALT, AST, ROS, T-AOC, MDA, GR, ΔΨm, and related proteins affected by ZO had been detected to validate the above mechanisms using dual cell models.

ZO could protect the L02 cells against ALI by regulating the PI3K/Akt/FoxO1 pathway, as well as restore the function of mitochondria and redox imbalance damaged by toxicants. This work has uncovered the nonimmune mechanisms of ZO against ALI to provide the basis for relevant research and disease treatment.

ZO could protect the L02 cells against ALI by regulating the PI3K/Akt/FoxO1 pathway, as well as restore the function of mitochondria and redox imbalance damaged by toxicants. This work has uncovered the nonimmune mechanisms of ZO against ALI to provide the basis for relevant research and disease treatment.

Metastasis is the leading cause of death in patients with colorectal cancer (CRC). The 5-year survival rate of CRC patients in whom the cancer has spread to distant sites is 13.5%. The most common sites of CRC metastasis are liver and lung. The principal therapies for CRC metastatic disease are surgery, but its benefits are limited.

This study aimed to reveal the regulatory mechanism of berberine on secondary homing of CRC cells to form metastatic focus. This was more valuable than the previous direct study of the migration and metastasis characteristics of CRC cells.

In this study, we used the functional enrichment analysis of differentially expressed genes after berberine treatment and investigated co-expression modules related with CRC metastasis by WGCNA. PPI and survival analyses of significant modules were also conducted. The biological functions of berberine in CRC lung and liver metastasis were investigated by a series of in vitro and in vivo experiments MTT, colony formation and mouse tail veine expression of hub gene HEY2 and metastasis related proteins E-cadherin and β-catenin and Cyclin D1 during MET in CRC lung and liver metastases. In total, HEY2 was a promising candidate biomarker for prognosis and molecular characteristics in CRC metastasis.

We revealed that berberine could significantly inhibit the expression of hub gene HEY2 and metastasis related proteins E-cadherin and β-catenin and Cyclin D1 during MET in CRC lung and liver metastases. In total, HEY2 was a promising candidate biomarker for prognosis and molecular characteristics in CRC metastasis.Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization - tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40-59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20-39 and 40-59 year age groups (P less then 0.05 and P less then 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P less then 0.