Yak genome database: a multi-omics analysis platform.

BACKGROUND: The yak (Bos grunniens) is a large ruminant species that lives in high-altitude regions and exhibits excellent adaptation to the plateau environments. To further understand the genetic characteristics and adaptive mechanisms of yak, we have developed a multi-omics database of yak including genome, transcriptome, proteome, and DNA methylation data. DESCRIPTION: The Yak Genome Database ( http://yakgenomics.com/ ) integrates the research results of genome, transcriptome, proteome, and DNA methylation, and provides an integrated platform for researchers to share and exchange omics data. The database contains 26,518 genes, 62 transcriptomes, 144,309 proteome spectra, and 22,478 methylation sites of yak. The genome module provides access to yak genome sequences, gene annotations and variant information. The transcriptome module offers transcriptome data from various tissues of yak and cattle strains at different developmental stages. The proteome module presents protein profiles from diverse yak organs. Additionally, the DNA methylation module shows the DNA methylation information at each base of the whole genome. Functions of data downloading and browsing, functional gene exploration, and experimental practice were available for the database. CONCLUSION: This comprehensive database provides a valuable resource for further investigations on development, molecular mechanisms underlying high-altitude adaptation, and molecular breeding of yak.

Genome-wide comparison of DNA methylation patterns between yak and three cattle strains and their potential association with mRNA transcription.

Yak has evolved specific adaptative mechanisms to high-altitude environment. Up to date, only a few studies reported the DNA methylation in yak. In the present study, genome-wide DNA methylome and transcriptome profiles in lung, mammary, and biceps brachii muscle tissues were compared between yak and three cattle breeds (Tibetan cattle, Sanjiang cattle, and Holstein cattle). The association between differentially expressed genes (DEGs) and differentially methylated regions (DMRs) was analyzed, and the biological functions of DEGs potentially driven by DMRs were explored by KEGG enrichment analysis. Finally, we found that yak-specific DMRs-driven DEGs were mainly involved in neuromodulation, respiration, lung development, blood pressure regulation, cardiovascular protection, energy metabolism, DNA repair, and immune functions. The higher levels of the key genes associated with these functions were observed in yak than in cattle, suggesting that DNA methylation might regulate these genes. Overall, the present study contributes basic data at the DNA methylation level to further understand the physiological metabolism in yak.

Immune response and protective efficacy of mannosylated polyethylenimine (PEI) as an antigen delivery vector, administered with a Streptococcus agalactiae DNA vaccine in Nile tilapia (Oreochromis niloticus).

This study examined the effectiveness of a DNA vaccine for S. agalactiae that was delivered by mannose-based polyethyleneimine (Man-PEI). The results showed that Man-PEI/pcDNA-Sip stimulated a higher serum antibody titer compared to control or other vaccine groups (p < 0.05). Additionally, it induced higher expression of immune-related genes, and increased activities of superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (AKP). Furthermore, the Man-PEI/pcDNA-Sip group showed an improved relative percent survival (RPS) of 85.71%. These results demonstrate the potential value of Man-PEI as a vaccine delivery vehicle, and suggest that it can be effective in boosting the immune protective rate induced by pcDNA-Sip vaccines.

Metformin exposure altered intestinal microbiota composition and metabolites in amphibian larvae.

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 µg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Dynamic alterations in yak (Bos grunniens) rumen microbiome in response to seasonal variations in diet.

Rumen microorganisms play important roles in the healthy growth of yaks. This study investigated changes in yak rumen microbiome during natural grazing at the warm seasons and supplementary feeding at cold seasons. High-throughput sequencing of 16S rRNA and metagenome analysis were conducted to investigate the structures and functions of yak rumen microbial communities. The results indicated that Bacteroidetes and Firmicutes were the most abundant phyla. In addition, Bacteroidetes might play a more important role than Firmicutes during the supplementary feeding stage (spring and winter), but less during natural grazing stage (summer and autumn). KEGG analysis showed that the amino sugar and nucleotide sugar metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, starch and sucrose metabolism, and fructose and mannose metabolism were the main pathways in the microbial community, which were significantly different between seasons. The carbohydrate-active enzymes (CAZyme) annotation revealed that cellulose was an important carbon source for microorganisms in yak rumen. Glycoside hydrolases (GHs) were the most abundant class of CAZymes, followed by glycosyl transferases (GTs), which were important to digestion of oil, cellulose, and hemicellulose in food. These results contribute to the understanding of microbial components and functions in yak rumen.

Genome-wide identification of SNPs associated with body weight in yak.

BACKGROUND: The yak is the most important livestock in the Qinghai-Tibet Plateau, and body weight directly affects the economic values of yak. Up to date, the genome-wide profiling of single-nucleotide polymorphisms (SNPs) associating with body weight has not been reported in yak. In the present study, the SNPs in 480 yaks from three breeds were analyzed using the commercial high-density (600 K) yak SNP chips. RESULTS: The results identified 12 and 4 SNPs potentially associated with body weight in male and female yaks, respectively. Among them, 9 and 2 SNPs showed significant difference in yak body weight between different genotypes at each locus in male and female yaks, respectively. Further exploration found 33 coding genes within the 100 kbp upstream or downstream to the SNP loci, which might be potentially affected by the variation of SNPs. Among them, G protein-coupled receptor kinase 4 (GRK4) might be potentially affected by the SNP AX-174555047, which has been reported to affect the functioning of two body-weight associated hormones (parathyroid hormone, PTH, and adrenomedullin, ADM). Determination of PTH and ADM levels in yak revealed positive relationship between PTH level and body weight, negative relationship between ADM level and body weight along with the variation of AX-174555047 mutation. CONCLUSIONS: These results suggested that the SNP AX-174555047 might potentially affect body weight through mediating GRK4 expression and then PTH and ADM functioning. Thus, the SNP AX-174555047 might be used as a biomarker for molecular breeding of yak. More investigations are required to validate this point.

Observational Insights into Isoprene Secondary Organic Aerosol Formation through the Epoxide Pathway at Three Urban Sites from Northern to Southern China.

Isoprene is the most abundant precursor of global secondary organic aerosol (SOA). The epoxide pathway plays a critical role in isoprene SOA (iSOA) formation, in which isoprene epoxydiols (IEPOX) and/or hydroxymethyl-methyl-α-lactone (HMML) can react with nucleophilic sulfate and water producing isoprene-derived organosulfates (iOSs) and oxygen-containing tracers (iOTs), respectively. This process is complicated and highly influenced by anthropogenic emissions, especially in the polluted urban atmospheres. In this study, we took a 1-year measurement of the paired iOSs and iOTs formed through the IEPOX and HMML pathways at the three urban sites from northern to southern China. The annual average concentrations of iSOA products at the three sites ranged from 14.6 to 36.5 ng m-3. We found that the nucleophilic-addition reaction of isoprene epoxides with water dominated over that with sulfate in the polluted urban air. A simple set of reaction rate constant could not fully describe iOS and iOT formation everywhere. We also found that the IEPOX pathway was dominant over the HMML pathway over urban regions. Using the kinetic data of IEPOX to estimate the reaction parameters of HMML will cause significant underestimation in the importance of HMML pathway. All these findings provide insights into iSOA formation over polluted areas.

Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro.

BACKGROUND: Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV. METHODS: A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 µg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT-PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated. RESULTS: Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells. CONCLUSIONS: Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.

Differences in proteomic profiles between yak and three cattle strains provide insights into molecular mechanisms underlying high-altitude adaptation.

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.

Whole-genome resequencing provides insights into the evolution and divergence of the native domestic yaks of the Qinghai-Tibet Plateau.

BACKGROUND: On the Qinghai-Tibet Plateau, known as the roof ridge of the world, the yak is a precious cattle species that has been indispensable to the human beings living in this high-altitude area. However, the origin of domestication, dispersal route, and the divergence of domestic yaks from different areas are poorly understood. RESULTS: Here, we resequenced the genome of 91 domestic yak individuals from 31 populations and 1 wild yaks throughout China. Using a population genomics approach, we observed considerable genetic variation. Phylogenetic analysis suggested that the earliest domestications of yak occurred in the south-eastern QTP, followed by dispersal to the west QTP and northeast to SiChuang, Gansu, and Qinghai by two routes. Interestingly, we also found potential associations between the distribution of some breeds and historical trade routes such as the Silk Road and Tang-Tibet Ancient Road. Selective analysis identified 11 genes showing differentiation between domesticated and wild yaks and the potentially positively selected genes in each group were identified and compared among domesticated groups. We also detected an unbalanced pattern of introgression among domestic yak, wild yak, and Tibetan cattle. CONCLUSIONS: Our research revealed population genetic evidence for three groups of domestic yaks. In addition to providing genomic evidence for the domestication history of yaks, we identified potential selected genes and introgression, which provide a theoretical basis and resources for the selective breeding of superior characters and high-quality yak.

Signature of high altitude adaptation in the gluteus proteome of the yak.

Yak is the unique Bovidae species in the Qinghai-Tibetan Plateau. A previous proteomic study has compared the yak muscle tissue to one cattle strain using the isobaric tags for relative and absolute quantification approach. In this study, to further investigate the molecular mechanisms underlying yak adaptation, the proteomic profiles of gluteus were compared between yak and one moderate-altitude cattle strain (Tibetan cattle) and two low-altitude cattle strains (Holstein and Sanjiang cattle) using a label-free quantitative method. The comparisons identified 20, 364, 143 upregulated proteins and 4, 6, 37 downregulated proteins in yak, compared with Tibetan, Holstein, and Sanjiang cattle, respectively. Protein-protein interaction analysis indicated that these differentially expressed proteins were mainly related to "oxidative phosphorylation" and "electron transport chain." Further analysis revealed that NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11, NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4, cytochrome C oxidase subunit 6A2, mitochondrial and cytochrome c oxidase subunit NDUFA4 were all increased in the yak, suggesting that yak might increase mitochondrial capacity to sustain metabolic rates under high altitude conditions, which might be a long-term adaptive mechanism underlying adaptation to high altitude environments. Yak increased the level of thioredoxin reductase 2 to protect themselves from oxidative damages. Moreover, the increased expression levels of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform and caveolin-1 in yak suggested that yaks promoted glucose uptake for adaptation to high altitude. These results provided more information to better understand the molecular mechanisms underlying yak adaption.

[Effect of ginsenoside Rg_3 nanostructured lipid carrier modified by pullulan on promoting absorption and its anti-tumor evaluation in vitro].

Ginsenoside Rg_3 is widely used in clinical practice as an anti-tumor adjuvant drug, but its application is limited due to its poor oral absorption. In this study, we intended to construct a ginsenoside Rg_3 nanostructured lipid carrier modified by the pullulan(PUL-Rg_3-NLC) to improve the adhesion properties of ginsenoside Rg_3, promote the drug uptake and improve the anti-tumor efficacy. PUL-Rg_3-NLC was characterized by morphology, particle size and Zeta potential. In vivo adhesion characteristics were evaluated by oral gavage tests, and the results were verified from multiple perspectives in combination with in vitro uptake behavior and in vitro pharmacodynamics. The results showed that PUL-Rg_3-NLC, with a particle size of(102±1.89) nm, was characterized by gastric adhesion and could be retained in gastric tissues for a long time, and its uptake by BGC-823 cells was promoted mainly through the pathway mediated by the caveolin-mediated endocytosis. In vitro MTT, cell apoptosis, wound-healing assay and invasion assay all showed some anti-tumor effects. Therefore, PUL-Rg_3-NLC can significantly promote the adhesion of Rg_3 in the stomach, promote the uptake of drugs by gastric cancer cells, and improve the anti-tumor effect. This study can provide some reference for the adjuvant treatment of gastric cancer.

Transcriptional and metabolic rewiring of colorectal cancer cells expressing the oncogenic KRASG13D mutation.

BACKGROUND: Activating mutations in KRAS frequently occur in colorectal cancer (CRC) patients, leading to resistance to EGFR-targeted therapies. METHODS: To better understand the cellular reprogramming which occurs in mutant KRAS cells, we have undertaken a systems-level analysis of four CRC cell lines which express either wild type (wt) KRAS or the oncogenic KRASG13D allele (mtKRAS). RESULTS: RNAseq revealed that genes involved in ribosome biogenesis, mRNA translation and metabolism were significantly upregulated in mtKRAS cells. Consistent with the transcriptional data, protein synthesis and cell proliferation were significantly higher in the mtKRAS cells. Targeted metabolomics analysis also confirmed the metabolic reprogramming in mtKRAS cells. Interestingly, mtKRAS cells were highly transcriptionally responsive to EGFR activation by TGFα stimulation, which was associated with an unexpected downregulation of genes involved in a range of anabolic processes. While TGFα treatment strongly activated protein synthesis in wtKRAS cells, protein synthesis was not activated above basal levels in the TGFα-treated mtKRAS cells. This was likely due to the defective activation of the mTORC1 and other pathways by TGFα in mtKRAS cells, which was associated with impaired activation of PKB signalling and a transient induction of AMPK signalling. CONCLUSIONS: We have found that mtKRAS cells are substantially rewired at the transcriptional, translational and metabolic levels and that this rewiring may reveal new vulnerabilities in oncogenic KRAS CRC cells that could be exploited in future.

Direct growth of ordered PdCu and Co doped PdCu nanoparticles on graphene oxide based on a one-step hydrothermal method for ultrasensitive sensing of H2O2 in living cells.

Ordered PdCu and Co doped PdCu nanoparticles have been synthesized on graphene oxide (GO). The obtained Co-PdCu/GO composites were used to fabricate a H2O2 electrochemical sensor which exhibits an ultralow LOD (limit of detection) of 1.2 nM and an extra broad linear range of 5 nM-5.774 mM, and has been used to detect H2O2 in living cells successfully.

[Diagnosis and treatment of a local case of Taenia saginata infection in Zhejiang Province].

Objective: To diagnose and provide treatment for a local case of taenia infection in Zhejiang Province and identify the species of the worm. Methods: The information of disease onset, clinical feature and therapeutic process was collected and epidemiological investigation was carried out. The anal cellophane swab was used to detect the eggs. Areca and pumpkin seeds were used for deworming. Morphological observation, PCR amplification and sequencing of cytochrome C oxidase 1(COX1) gene were performed for the discharged worm. Results: The epidemiological results showed that the patient did not go outside Pujiang County in the past two years, and had no history of eating raw pork, beef or animal offal. But she often had barbecues and hot-pot food, occasionally with raw vegetables. Taenia eggs were found on her perianal skin. The discharged worm was suspected to be Taenia saginata or Taenia asiatica by morphological observation. PCR amplification of COX1 resulted in a band of 832 bp, which was 99%, 96% and 88% homologous to COX1 of Taenia saginata (GenBank accession number: AB107239.1), Taenia asiatica (GenBank accession number: AB107235.1) and Taenia solium (GenBank accession number: AB066485.1), respectively. Conclusion: According to the clinical feature, epidemiological information and sequencing results, this case is confirmed to be a local infection of Taenia saginata.

The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma.

RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.

[Unsupervised data mining for prescription and medication regularity for treatment of cervical vertigo].

Vertebral artery type cervical spondylosis is a common type of cervical spondylosis, also known as cervical vertigo. In recent years, with the increase of people's life pace and the number of office staff, the incidence rate has been rising year by year, with a trend of younger age. Because traditional Chinese medicine has unique advantages in treating cervical vertigo, it is necessary to study the regularity of the Chinese medicine for cervical vertigo. But at present, the research is mainly based on the statistics for frequency and proportion of herbs. In addition, in the process of diagnosis and treatment of Chinese medicine, personal experience also caused differences in prescription compatibility and drug dosage, which makes difficult guarantee for the safety and effectiveness of drug treatment. So, this paper is based on literatures about the traditional Chinese medicine in treatment of cervical vertigo in the past 5 years, by using association rules algorithm, complex system entropy clustering and other non supervised data mining methods. Analysis was made for the use of various drugs in the frequency, the association rules, the core drug combination and the new prescriptions. The traditional Chinese medicine inheritance support system(TCMISS) was utilized to analyze 154 drugs from the 101 prescriptions, determine the use frequency of drugs, analyze the characteristics and the compatibility of core drugs, and dig out 14 core drug combinations and 7 new prescription combinations. The prescription and medication regularities illustrates the drugs for treatment of cervical vertigo, including those for flating liver and suppressing yang, invigorating the circulation of blood to remove blood stasis, reducing water and permeating dampness, increasing qi and activating blood, and nourishing the liver and kidney mainly. Treatment rules are nourishing liver and kidney, invigorating the circulation of blood stasis Tongqiao, reducing phlegm and dampness, flating liver and suppressing yan, dredging collaterals, supplementing qi and nourishing blood. This study aims to summarize frequently used single herbs for vertebral artery type cervical spondylosis, combinations of frequently used herbs and dosage of frequently used herbs with significant efficacy, define the current prescription and medication regularities for treating cervical vertigo and give guidances for clinical mediation.

Chitosan-based multifunctional hydrogel with bio-adhesion and antioxidant properties for efficient wound hemostasis.

Benefiting from the biocompatibility, adhesiveness, and natural extracellular matrix-mimicking ability, hydrogels have received increasing research in recent years. In this study, a hydrogel system composed of dopamine, quaternized ammoniated chitosan (QCS), and polyvinylpyrrolidone was reported to exhibit fast hemostatic properties in Sprague-Dawley rat tail amputation and liver bleeding models. The results showed that this hydrogel had good hemostatic properties. The designed hydrogel showed high swelling ratios in H2O, PBS, and 0.9 % NaCl solution, indicating its capability to absorb tissue residual exudate and form a stable hydrogel. Compared with the control group, the blood loss in Sprague-Dawley rat tail amputation and liver bleeding were reduced by nearly 78 % and 76 %, respectively. Interestingly, dopamine endowed the hydrogel with antioxidant properties, thus holding a great application promise in inflammatory wounds. Furthermore, the designed hydrogel demonstrated good and reversible adhesion properties (12.23 ± 0.22 kPa-24.31 ± 0.55 kPa), ensuring its firm attachment to bleeding wounds of pig skin in wet environments. This research points out a novel path for designing chitosan-based hydrogels for biomedical applications.

Multidisciplinary approaches in the management of advanced hepatocellular carcinoma: Exploring future directions.

Recently, we read the article "Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of the literature" published in the World Journal of Gas trointestinal Oncology. The prognosis of advanced hepatocellular carcinoma (HCC) is poor, and multidisciplinary comprehensive treatment is currently the main research direction. This case report demonstrated the efficacy of the combination therapy of transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, epclusa, lenvatinib and sintilimab for a patient with advanced HCC, and the report can serve as a reference for clinical practice. We would also like to share some of our views.