BackgroundIn the pig production industry, artificial insemination (AI) plays an important role in enlarging the beneficial impact of elite boars. Understanding the genetic architecture and detecting genetic markers associated with semen traits can help in improving genetic selection for such traits and accelerate genetic progress. In this study, we utilized a weighted single-step genome-wide association study (wssGWAS) procedure to detect genetic regions and further candidate genes associated with semen traits in a Duroc boar population. Overall, the full pedigree consists of 5284 pigs (12 generations), of which 2693 boars have semen data (143,113 ejaculations) and 1733 pigs were genotyped with 50 K single nucleotide polymorphism (SNP) array.ResultsResults show that the most significant genetic regions (0.4 Mb windows) explained approximately 2%~ 6% of the total genetic variances for the studied traits. Totally, the identified significant windows (windows explaining more than 1% of total genetic variances) explained 28.29, 35.31, 41.98, and 20.60% of genetic variances (not phenotypic variance) for number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, respectively. Several genes that have been previously reported to be associated with mammal spermiogenesis, testes functioning, and male fertility were detected and treated as candidate genes for the traits of interest: Number of sperm cells, TDRD5, QSOX1, BLK, TIMP3, THRA, CSF3, and ZPBP1; Sperm motility, PPP2R2B, NEK2, NDRG, ADAM7, SKP2, and RNASET2; Sperm progressive motility, SH2B1, BLK, LAMB1, VPS4A, SPAG9, LCN2, and DNM1; Total morphological abnormalities, GHR, SELENOP, SLC16A5, SLC9A3R1, and DNAI2.ConclusionsIn conclusion, candidate genes associated with Duroc boars’ semen traits, including the number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, were identified using wssGWAS. KEGG and GO enrichment analysis indicate that the identified candidate genes were enriched in biological processes and functional terms may be involved into spermiogenesis, testes functioning, and male fertility.

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Meat quality is an important trait for pig-breeding programs aiming to meet consumers’ demands. Geneticists must improve meat quality based on their understanding of the underlying genetic mechanisms. Previous studies showed that most meat-quality indicators were low-to-moderate heritability traits; therefore, improving meat quality using conventional techniques remains a challenge. Here, we performed a genome-wide association study of meat-quality traits using the GeneSeek Porcine SNP50K BeadChip in 582 crossbred Duroc × (Landrace × Yorkshire) commercial pigs (249 males and 333 females). Meat conductivity, marbling score, moisture, meat color, pH, and intramuscular fat (IMF) content were investigated. The genome-wide association study was performed using both fixed and random model Circulating Probability Unification (FarmCPU) and a mixed linear model (MLM) with the rMVP software. The genomic heritability of the studied traits ranged from 0.13 ± 0.07 to 0.55 ± 0.08 for conductivity and meat color, respectively. Thirty-two single-nucleotide polymorphisms (SNPs) were identified for meat quality in the crossbred pigs using both FarmCPU and MLM. Among the detected SNPs, five, nine, seven, four, six, and five were significantly associated with conductivity, IMF, marbling score, meat color, moisture, and pH, respectively. Several candidate genes for meat quality were identified in the detected genomic regions. These findings will contribute to the ongoing improvement of meat quality, meeting consumer demands and improving the economic outlook for the swine industry.

The greenbug, Schizaphis graminum (Rondani), is one of the major pests of wheat worldwide. The efficient utilization of wheat genes expressing resistance to greenbug infestation is highly dependent on a clear understanding of their relationships. The use of such genes will be further facilitated through the use of molecular markers linked to resistance genes. The present study involved several F(2) wheat populations derived from crosses between susceptible cultivars and resistant germplasm carrying different greenbug resistance genes. These populations were used to characterize the inheritance of a wheat gene ( Gbz) conferring tolerance to greenbug biotype I, to identify molecular markers linked to Gbz, and to investigate the relationship between Gbz and Gb3, a previously identified greenbug resistance gene. Our results indicated that Gbz is inherited as a single dominant gene. Microsatellite marker Xwmc157 is completely linked to Gbz, and Xbarc53 and Xgdm46 flank Gbz at distances of 5.1 and 9.5 cM, respectively. Selection of Gbz using marker Xwmc157 alone gives breeders 100% selection accuracy. Gbz may be placed in the distal region of the long arm of the wheat chromosome 7D. The results of allelism tests indicated that Gbz is either allelic or tightly linked to Gb3.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used in patients with various cancers and have shown efficient therapeutic outcomes. However, fewer than 40% of cases across multiple cancer types show a response to ICIs. Therefore, developing more efficient combinational approaches with ICIs and revealing the underlying mechanisms are important goals for achieving rapid clinical transformation and application.MethodsThe effects on antitumor immunity activity of albendazole (ABZ) and the synergistic effects of ABZ with CD73 blockade were investigated in the melanoma B16F10 and the Lewis lung cancer tumor-bearing immune-competent mice models. The mechanism of ABZ reducing PD-L1 protein level through suppressing UBQLN4 was identified and validated through immunoprecipitation-mass spectrometry and molecular methods. Bioinformatics and anti-PD-1 therapy melanoma patients samples analysis were used to assess the level of UBQLN4/PD-L1 in the therapeutic efficacy of anti-PD-1 therapy.ResultsABZ induces CD8+ T cell activity and subsequent immunotherapy response associated with suppression of PD-L1 protein level. Mechanistically, we revealed that ABZ promotes ubiquitin-mediated degradation of PD-L1 via suppressing UBQLN4, which was bound to PD-L1 and stabilized PD-L1 protein. Preclinically, genetic deletion or target inhibition of CD73 showed synergistic effects with ABZ treatment in the immune-competent mice models. Significantly, UBQLN4 and PD-L1 levels were higher in the tumor region of responders versus non-responders and correlated with better progression-free survival and overall survival in anti-PD-1 therapy melanoma patients.ConclusionsOur findings revealed a previously unappreciated role of ABZ in antitumor immunity by inducing ubiquitin-mediated PD-L1 protein degradation, identified predictors for assessing the therapeutic efficacy of anti-PD-1 therapy, and provided novel therapeutic possibility by combination treatment of ABZ and CD73 blockade in cancers.

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Background The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration. Methods RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The “survival” and “survminer” packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis. Results Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT. Conclusions MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.

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