Summary Under natural farming, environmental pathogenic microorganisms may invade and affect swine lungs, further resulting in lung lesions. However, few studies on swine lung microbiota and their potential relationship with lung lesions were reported. Here, we sampled 20 pigs from a hybrid herd raised under natural conditions; we recorded a lung‐lesion phenotype and investigated lung microbial communities by sequencing the V3‐V4 region of 16S rRNA gene for each individual. We found reduced microbial diversity but more biomass in the severe‐lesion lungs. Methylotenera , Prevotella , Sphingobium and Lactobacillus were the prominent bacteria in the healthy lungs, while Mycoplasma , Ureaplasma , Sphingobium , Haemophilus and Phyllobacterium were the most abundant microbes in the severe‐lesion lungs. Notably, we identified 64 lung‐lesion‐associated OTU s, of which two classified to Mycoplasma were positively associated with lung lesions and 62 showed negative association including thirteen classified to Prevotella and six to Ruminococcus . Cross‐validation analysis showed that lung microbiota explained 23.7% phenotypic variance of lung lesions, suggesting that lung microbiota had large effects on promoting lung healthy. Furthermore, 22 KEGG pathways correlated with lung lesions were predicted. Altogether, our findings improve the knowledge about swine lung microbial communities and give insights into the relationship between lung microbiota and lung lesions.
Hypothyroidism is found to be associated with severity of OSA. However, obesity can be a confounder in the outcomes observed herein.
The mutation rate used in the previous analyses of pig evolution and demographics was cursory and hence invited potential bias in inferring evolutionary history. Herein, we estimated the de novo mutation rate of pigs as 3.6 × 10−9 per base per generation using high-quality whole-genome sequencing data from nine individuals in a three-generation pedigree through stringent filtering and validation. Using this mutation rate, we re-investigated the evolutionary history of pigs. The estimated divergence time of ∼ 10 kiloyears ago (KYA) between European wild and domesticated pigs was consistent with the domestication time of European pigs based on archaeological evidence. However, other divergence events inferred here were not as ancient as previously described. Our estimates suggest that Sus speciation occurred ∼ 1.36 million years ago (MYA); European wild pigs split from Asian wild pigs only ∼ 219 KYA; and south and north Chinese wild pigs split ∼ 25 KYA. Meanwhile, our results showed that the most recent divergence event between Chinese wild and domesticated pigs occurred in the Hetao Plain, northern China, approximately 20 KYA, supporting the possibly independent domestication in northern China along the middle Yellow River. We also found that the maximum effective population size of pigs was ∼ 6 times larger than estimated before. An archaic migration from other Sus species originating ∼ 2 MYA to European pigs was detected during western colonization of pigs, which may affect the accuracy of previous demographic inference. Our de novo mutation rate estimation and its consequences for demographic history inference reasonably provide a new vision regarding the evolutionary history of pigs.
The refractory of castration-resistant prostate cancer (CRPC) is mainly reflected in drug resistance. The current research on the resistance mechanism of CRPC is still in its infancy. In this study, we revealed for the first time the key role of LncRNA PCBP1-AS1 in CRPC drug resistance. Through detailed in vivo and in vitro studies, we found that PCBP1-AS1 may enhance the deubiquitination of AR/AR-V7 by stabilizing the USP22-AR/AR-V7 complex, thereby preventing AR/AR-V7 from being degraded through the ubiquitin–proteasome pathway. Targeting PCBP1-AS1 can significantly restore the drug sensitivity of enzalutamide-resistant tumors in vivo and in vitro. Our research further expands the function of LncRNA in castration-resistant prostate cancer, which may provide new potential for clinical diagnosis and targeted therapy.
Castration-resistant prostate cancer (CRPC) is a highly malignant type of advanced cancer resistant to androgen deprivation therapy. One of the important mechanisms for the development of CRPC is the persistent imbalanced regulation of AR and AR splice variants (AR/AR-Vs). In this study, we reported KDM4A-AS1, a recently discovered lncRNA, as a tumor promoter that was significantly increased in CRPC cell lines and cancer tissues. Depletion of KDM4A-AS1 significantly reduced cell viability, proliferation, migration in vitro, and tumor growth in vivo. We found that by binding to the NTD domain, KDM4A-AS1 enhances the stability of USP14-AR/AR-Vs complex, and promoted AR/AR-Vs deubiquitination to protect it from MDM2-mediated ubiquitin-proteasome degradation. Moreover, KDM4A-AS1 was found to enhance CRPC drug resistance to enzalutamide by repressing AR/AR-Vs degradation; antisense oligonucleotide drugs targeting KDM4A-AS1 significantly reduced the growth of tumors with enzalutamide resistance. Taken together, our results indicated that KDM4A-AS1 played an important role in the progression of CRPC and enzalutamide resistance by regulating AR/AR-Vs deubiquitination; targeting KDM4A-AS1 has broad clinical application potential.
Background Short tandem repeats (STRs) are genetic markers with a greater mutation rate than single nucleotide polymorphisms (SNPs) and are widely used in genetic studies and forensics. However, most studies in pigs have focused only on SNPs or on a limited number of STRs. Results This study screened 394 deep-sequenced genomes from 22 domesticated pig breeds/populations worldwide, wild boars from both Europe and Asia, and numerous outgroup Suidaes, and identified a set of 878,967 polymorphic STRs (pSTRs), which represents the largest repository of pSTRs in pigs to date. We found multiple lines of evidence that pSTRs in coding regions were affected by purifying selection. The enrichment of trinucleotide pSTRs in coding sequences (CDS), 5′UTR and H3K4me3 regions suggests that trinucleotide STRs serve as important components in the exons and promoters of the corresponding genes. We demonstrated that, compared to SNPs, pSTRs provide comparable or even greater accuracy in determining the breed identity of individuals. We identified pSTRs that showed significant population differentiation between domestic pigs and wild boars in Asia and Europe. We also observed that some pSTRs were significantly associated with environmental variables, such as average annual temperature or altitude of the originating sites of Chinese indigenous breeds, among which we identified loss-of-function and/or expanded STRs overlapping with genes such as AHR, LAS1L and PDK1. Finally, our results revealed that several pSTRs show stronger signals in domestic pig—wild boar differentiation or association with the analysed environmental variables than the flanking SNPs within a 100-kb window. Conclusions This study provides a genome-wide high-density map of pSTRs in diverse pig populations based on genome sequencing data, enabling a more comprehensive characterization of their roles in evolutionary and environmental adaptation.
This study focused on large-scale roof-fall accidents occurred in large-section coal seam roadways of Bayangaole Coal Mine, Inner Mongolia, China, and investigated the occurrence mechanism of roof-fall and the related supporting control method in detail. Firstly, the fracture characteristics of the surrounding rocks on the roadway roof were measured using a stratum detector. The results showed that the roadway roof underwent the most severe failure with a maximum deformation of 3.53 m; the bedding separation and fracture zones were distributed at irregular intervals. Accordingly, the entire stratum was separated into several thin sublayers, significantly reducing the stability of roof. In addition, the roof medium grained sandstone of roadway is water-rich strata, and water aggravates the damage of roof. Next, the mechanism of the occurrence of roof-fall accidents in the roadway was elucidated in detail. The following three reasons are mainly attributed to the occurrence of roof-fall accidents: (i) effects of mining-induced stress and tectonic stress, (ii) existence of equipment cavern on the side of roadway, and (iii) unreasonable support parameters. On that basis, a new supporting design is proposed, including a more reasonable arrangement of anchor cables and bolts, bolts with full-length anchorage which are applicable in cracked and water-rich roadway, high-strength anchor cables, and crisscrossed steel bands. Moreover, high pretightening force was applied. Finally, a field test was performed, and the mining-induced roof displacement and stress on anchor cable (bolt) were monitored in the test section. The maximum roof displacements at the two monitoring sections were 143 mm and 204 mm, respectively, far smaller than the roadway’s allowable deformation. Moreover, the stress on roof anchor cables (bolts) was normal, and no anchorage-dragging and tensile failure phenomena were observed. The monitoring data indicated that the new supporting design was remarkable on the control of large-section coal seam roadway roof deformation.
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