Essential oils (EO) are secondary metabolites usually made up of terpenoids and phenylpropanoids and have antimicrobial properties. However, the feeding effects of EO-Cobalt (EOC) on the performance of goats are largely unknown. Herein we investigated and reported the effects of dietary EOC (0, 52, and 91 mg daily) on fiber producing cashmere goats. We determined the resulting phenotypes including live growth, carcass weight, meat quality, and cashmere fiber traits. We show that dietary supplement of EOC significantly promoted average daily gain (P < 0.05), and significantly improved carcass weight, and meat and hair fiber quality (P < 0.05). We further conducted RNA-seq using skin and liver tissues from each group to assess the molecular mechanism conferring these phenotypic changes. A total of 191 differentially expressed genes were found in the skin tissues (0 vs 91 mg), while 1,127 DEGs were found in livers. Analyses of liver samples for differential gene action and functional prediction found that EOC stimulated physiological changes in the body's immune system at both blood and cell levels. Our results demonstrated the potential of using EO-based feed ingredient to improve animal growth performance, meat quality and fiber quality, and further illustrated the molecular basis that contribute to phenotypes at physiological levels.
Background Transcriptional regulatory network (TRN) is used to study conditional regulatory relationships between transcriptional factors and genes. However few studies have tried to integrate genomic variation information such as copy number variation (CNV) with TRN to find causal disturbances in a network. Intrahepatic cholangiocarcinoma (ICC) is the second most common hepatic carcinoma with high malignancy and poor prognosis. Research about ICC is relatively limited comparing to hepatocellular carcinoma, and there are no approved gene therapeutic targets yet. Method We first constructed TRN of ICC (ICC-TRN) using forward-and-reverse combined engineering method, and then integrated copy number variation information with ICC-TRN to select CNV-related modules and constructed CNV-ICC-TRN. We also integrated CNV-ICC-TRN with KEGG signaling pathways to investigate how CNV genes disturb signaling pathways. At last, unsupervised clustering method was applied to classify samples into distinct classes. Result We obtained CNV-ICC-TRN containing 33 modules which were enriched in ICC-related signaling pathways. Integrated analysis of the regulatory network and signaling pathways illustrated that CNV might interrupt signaling through locating on either genomic sites of nodes or regulators of nodes in a signaling pathway. In the end, expression profiles of nodes in CNV-ICC-TRN were used to cluster the ICC patients into two robust groups with distinct biological function features. Conclusion Our work represents a primary effort to construct TRN in ICC, also a primary effort to try to identify key transcriptional modules based on their involvement of genetic variations shown by gene copy number variations (CNV). This kind of approach may bring the traditional studies of TRN based only on expression data one step further to genetic disturbance. Such kind of approach can easily be extended to other disease samples with appropriate data.
Abstract CRISPR/Cas enhanced correction of the sickle cell disease (SCD) genetic defect in patient-specific induced Pluripotent Stem Cells (iPSCs) provides a potential gene therapy for this debilitating disease. An advantage of this approach is that corrected iPSCs that are free of off-target modifications can be identified before differentiating the cells into hematopoietic progenitors for transplantation. In order for this approach to be practical, iPSC generation must be rapid and efficient. Therefore, we developed a novel helper-dependent adenovirus/Epstein-Barr virus (HDAd/EBV) hybrid reprogramming vector, rCLAE-R6, that delivers six reprogramming factors episomally. HDAd/EBV transduction of keratinocytes from SCD patients resulted in footprint-free iPSCs with high efficiency. Subsequently, the sickle mutation was corrected by delivering CRISPR/Cas9 with adenovirus followed by nucleoporation with a 70 nt single-stranded oligodeoxynucleotide (ssODN) correction template. Correction efficiencies of up to 67.9% (β A /[β S +β A ]) were obtained. Whole-genome sequencing (WGS) of corrected iPSC lines demonstrated no CRISPR/Cas modifications in 1467 potential off-target sites and no modifications in tumor suppressor genes or other genes associated with pathologies. These results demonstrate that adenoviral delivery of reprogramming factors and CRISPR/Cas provides a rapid and efficient method of deriving gene-corrected, patient-specific iPSCs for therapeutic applications.
Abnormally high activation of transforming growth factor-β (TGF-β) signaling has been demonstrated to be involved in the initiation and progression of keloids. However, the functional role of long non-coding RNA (lncRNA)-activated by TGF-β (lncRNA-ATB) in keloids has not been documented. Here we investigated the role of lncRNA-ATB in the autocrine secretion of TGF-β in keloid fibroblasts (KFs) and explored the underlying molecular mechanism. Using immunohistochemistry and quantitative RT-PCR analysis, we showed that lncRNA-ATB and ZNF217, a transcriptional activator of TGF-β, were overexpressed and miR-200c, which targets ZNF217, was under-expressed in keloid tissue and keloid fibroblasts. Through gain- and loss-of-function studies, we demonstrated that knockdown of lncRNA-ATB decreased autocrine secretion of TGF-β2 and ZNF217 expression but upregulated expression of miR-200c in KFs. Stable downregulation of ZNF217 expression decreased the autocrine secretion of TGF-β2. miR-200c was endogenously associated with lncRNA-ATB, and inhibition of miR-200c overcame the decrease in ZNF217 expression in KFs. Taken together, these findings indicate that lncRNA-ATB governs the autocrine secretion of TGF-β2 in KFs, at least in part, by downregulating the expression level of ZNF217 via miR-200c, suggesting a signaling axis consisting of lncRNA-ATB/miR-200c/ZNF217/TGF-β2. These findings may provide potential biomarkers and targets for novel diagnostic and therapeutic approaches for keloids.
Ankylosing spondylitis (AS; MIM 106300) is a common rheumatic disease with strong genetic components affecting approximately 0.3% of the population. The exact genetic mechanism of AS remains elusive. Our previous study showed that AS could be transmitted in an autosomal dominant inheritance mode and a 6-cM candidate region located on the chromosome 2q36.1-36.3 was mapped in a Chinese family. Mutation screening was conducted within the candidate region in the family and other AS by sequencing, and the novel mutation will be further validated in other AS families, sporadic cases and healthy controls by mass spectrometry. We identified a rare non-synonymous mutation (Arg580Gly) in insulin receptor substrate 1 (IRS1) co-segregated with disease phenotype in patients of the family, which was not found in other AS families, sporadic patients and healthy controls. In the study, we found a rare non-synonymous mutation in IRS1 co-segregation in one Chinese family with AS, which indicated a new candidate disease causative gene for AS.
In the process of green and smart mine construction under the context of carbon neutrality, China's coal safety situation has been continuously improved in recent years. In order to recognize the development of coal production in China and prepare for future monitoring and prevention of safety incidents, this study mainly elaborated on the basic situation of coal resources and national mining accidents over the past five years (2017-2021), from four dimensions (accident level, type, region, and time), and then proposed the preventive measures based on accident statistical laws. The results show that the storage of coal resources has obvious geographic characteristics, mainly concentrated in the Midwest, with coal resources in Shanxi and Shaanxi accounting for about 49.4%. The proportion of coal consumption has dropped from 70.2% to 56% between 2011 and 2021, but still accounts for more than half of the all. Meanwhile, the accident-prone areas are positively correlated with the amount of coal production. Among different levels of coal mine accidents, general accidents had the highest number of accidents and deaths, with 692 accidents and 783 deaths, accounting for 87.6% and 54.64% respectively. The frequency of roof, gas, and transportation accidents is relatively high, and the number of single fatalities caused by gas accidents is the largest, about 4.18. In terms of geographical distribution of accidents, the safety situation in Shanxi Province is the most severe. From the time distribution of coal mine accidents, the accidents mainly occurred in July and August, and rarely occurred in February and December. Finally, the "4 + 4" safety management model is proposed, combining the statistical results with coal production in China. Based on the existing health and safety management systems, the managements are divided into four sub-categories, and more specific measures are suggested.
Dehydrins (DHNs) play a crucial role in enhancing abiotic stress tolerance in plants. Although DHNs have been identified and characterized in many plants, there is little known about Capsicum annuum L., one of the economically important vegetable crops. In this study, seven CaDHNs in the pepper genome were identified, which could be divided into two classes: YnSKn- and SKn-type, based on their highly conserved domains. Quantitative real-time PCR (qRT-PCR) results showed that the seven DHN genes were expressed in all tissues and might be involved in the growth and development of pepper. The gene expression profiles analysis suggested that most of the CaDHN genes were induced by various stresses (low temperature, salt and mannitol) and signaling molecules (ABA, SA and MeJA). Furthermore, the CaDHN3 (YSK2)-silenced pepper plants showed obvious lower resistance to abiotic stresses (cold, salt and mannitol) than the control plants (TRV2:00). So the CaDHN3 might act as a positive role in resisting abiotic stresses. This study lays the foundation for further studies into the regulation of their expression under various conditions.
The gut microbiota composition is influenced by the diet as well as the environment in both wild and domestic animals. We studied the effects of two feeding systems on the rumen and hindgut microbiome of semi-feral Tibetan goats kept at high altitude (∼4800 m) using 16S rRNA gene and metagenomic sequencing. Intensive drylot feeding resulted in significantly higher zootechnical performance, narrower ruminal acetate: propionate ratios and a drop in the average rumen pH at slaughter to ∼5.04. Hindgut microbial adaption appeared to be more diverse in the drylot group suggesting a higher influx of undegraded complex non-starch polysaccharides from the rumen. Despite their higher fiber levels in the diet, grazing goats exhibited lower counts of Methanobrevibacter and genes associated with the hydrogenotrophic methanogenesis pathway, presumably reflecting the scarce dietary conditions (low energy density) when rearing goats on pasture from extreme alpine environments. These conditions appeared to promote a relevant abundance of bacitracin genes. In parallel, we recognized a significant increase in the abundance of antibiotic resistance genes in the digestive tracts of drylot animals. In summary, this study provides a deeper insight into the metataxonomic and functional adaption of the gastrointestinal microbiome of goats subject to intensive drylot and extensive pasture rearing conditions at high altitude.
Further improvements to the yield potential of Chinese milk vetch seed are essential for the planting demand of green manure. Flower and pod development directly determines the number of seeds and the seed yield of Chinese milk vetch. However, the accumulation and translocation of dry matter and nitrogen between plant organs directly affects flower and pod development and morphological formation. There are few studies that analyse the relationship between the accumulation and transport of dry matter and nitrogen and the number of flowers, pods, grains and seed yield during Chinese milk vetch’s critical development period. This study aimed to determine the seed yield response to dry matter and nitrogen accumulation and translocation during the Chinese milk vetch growth period and to quantify the relationship between these factors to predict Chinese milk vetch seed yield. Experiments were performed during the 2017–2018 and 2018–2019 growing seasons at the Dayuzhuang experimental field. The first experiment involved five foliar application stages (late wintering stage, returning green stage, squaring stage, pre-flowering stage, and 5 days after flowering) and six foliar application concentrations of borate solution (0, 500, 1000, 2000, 4000, and 6000 mg L -1 ). Experiment 2 included five foliar application stages (late wintering stage, returning green stage, squaring stage, pre-flowering stage, and 5 days after flowering) and six foliar application concentrations of paclobutrazol (0, 200, 300, 400, 500, and 600 mg L -1 ). When the dry matter mass in the full flowering stage was 3500–4500 kg hm -2 , the seed yield reached more than 800 kg hm -2 . When the translocated assimilates were stored in the vegetative organs before flowering, the assimilate translocation rate and their contributions to seed yield were 1500–1800 kg hm -2 , 30–35%, and 28–38%, respectively, and the Chinese milk vetch seed yield was predicted to reach 800–1000 kg hm -2 at maturity. When the nitrogen translocation amount in the vegetative organs before flowering, the nitrogen translocation rate, and the contribution rate to the seed yield were 68–78 kg hm -2 , 65–75%, and 75–85%, respectively, the Chinese milk vetch seed yield was predicted to reach 800–1000 kg hm -2 at maturity. If the accumulation and translocation index values of dry matter and nitrogen were lower or higher than the above ranges, the seed yield was lower than 800 kg hm -2 . The results of this study revealed the mechanism by which dry matter and nitrogen accumulation and translocation affect the Chinese milk vetch seed yield. These findings enrich the seed yield formation theory of Chinese milk vetch. They provide an early determination and quantitative regulation of high and stable seed yield for Chinese milk vetch in the field and aid researchers to integrate multiple production technologies for the sustainable production of Chinese milk vetch.
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