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To fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.
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Bases de Dados Genéticas , Suínos , Animais , Estudo de Associação Genômica Ampla , Genótipo , Herança Multifatorial , Fenótipo , Suínos/genética , MultiômicaRESUMO
OBJECTIVE: The use of a flow diverter (FD) in the treatment of ruptured aneurysms is limited due to the increased risk of perioperative ischemia and hemorrhagic complications. Adjunctive coil embolization and an evidence-based antithrombotic regimen may improve therapeutic safety, although evidence from relevant clinical research is limited. The authors' aim was to further assess the perioperative safety and long-term efficacy of this strategy. METHODS: Data on patients with FD insertion and coil embolization were collected retrospectively at two centers. The perioperative antithrombotic regimen consists of intraoperative tirofiban and continues for 24 hours postoperatively, with the initiation of an orally administered dual-antiplatelet regimen 4 hours prior to tirofiban cessation, rather than purposeful preoperative antiplatelet therapy. Perioperative cerebral ischemia and hemorrhagic complications and long-term aneurysm occlusion rates were recorded to evaluate the safety and efficacy of the procedure, respectively. RESULTS: In total, 67 cases were screened and 41 cases were ultimately included in this study. A total of 2 cases (4.9%) of perioperative cerebral hemorrhagic events occurred, 1 of which (2.4%) was attributable to rerupture of the aneurysm. Cerebral ischemic events were reported in 3 patients, including 1 with cortical thromboembolism and 2 with perforator occlusion of the basilar artery. A median 8-month follow-up was attained in 25 patients (61.0%), with a 92% complete or near-complete occlusion rate. CONCLUSIONS: FD insertion combined with coil embolization is a potentially safe and effective therapeutic strategy for ruptured aneurysms when accompanied with perioperative evidence-based antithrombotic therapy.
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Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Doenças Vasculares , Humanos , Tirofibana , Fibrinolíticos , Estudos Retrospectivos , Resultado do Tratamento , Aneurisma Intracraniano/cirurgia , Embolização Terapêutica/métodos , Aneurisma Roto/etiologia , Doenças Vasculares/etiologia , Stents/efeitos adversos , Procedimentos Endovasculares/métodosRESUMO
Circular RNAs (circRNAs) are a class of non-coding RNAs with diverse functions, and previous studies have reported that circRNAs are involved in the growth and development of pigs. However, studies about porcine circRNAs over the past few years have focused on a limited number of tissues. Based on 215 publicly available RNA sequencing (RNA-seq) samples, we conducted a comprehensive analysis of circRNAs in nine pig tissues, namely, the gallbladder, heart, liver, longissimus dorsi, lung, ovary, pituitary, skeletal muscle, and spleen. Here, we identified a total of 82,528 circRNAs and discovered 3818 novel circRNAs that were not reported in the CircAtlas database. Moreover, we obtained 492 housekeeping circRNAs and 3489 tissue-specific circRNAs. The housekeeping circRNAs were enriched in signaling pathways regulating basic biological tissue activities, such as chromatin remodeling, nuclear-transcribed mRNA catabolic process, and protein methylation. The tissue-specific circRNAs were enriched in signaling pathways related to tissue-specific functions, such as muscle system process in skeletal muscle, cilium organization in pituitary, and cortical cytoskeleton in ovary. Through weighted gene co-expression network analysis, we identified 14 modules comprising 1377 hub circRNAs. Additionally, we explored circRNA-miRNA-mRNA networks to elucidate the interaction relationships between tissue-specific circRNAs and tissue-specific genes. Furthermore, our conservation analysis revealed that 19.29% of circRNAs in pigs shared homologous positions with their counterparts in humans. In summary, this extensive profiling of housekeeping, tissue-specific, and co-expressed circRNAs provides valuable insights into understanding the molecular mechanisms of pig transcriptional expression, ultimately deepening our understanding of genetic and biological processes.
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MicroRNAs , RNA Circular , Humanos , Feminino , Animais , Suínos/genética , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , RNA Mensageiro/genética , Perfilação da Expressão Gênica , Músculo Esquelético/metabolismoRESUMO
It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. Whole genome bisulfite sequencing (WGBS) is able to generate the sequencing data of DNAs, and shows the potential ability to detect CNVs. However, the evaluations and performances on the detections of CNVs using WGBS data is still unclear. In this study, five software with different strategies for CNV detections, e.g., BreakDancer, cn.mops, CNVnator, DELLY and Pindel, were selected to explore and benchmark the performances of CNV detections with WGBS data. Based on the real (2.62 billion reads) and simulated (12.35 billion reads) WGBS data of humans, we calculated the number, precision, recall, relative ability, memory usage, and running time of CNV detections by 150 times, and tried to figure out the optimal strategy for CNV detections with WGBS data. Based on the real WGBS data, Pindel detected the most deletions and duplications, CNVnator detected the deletions with the highest precision, cn.mops detected the duplications with the highest precision, Pindel detected the deletions with the highest recall, and cn.mops detected the duplications with the highest recall. Based on the simulated WGBS data, BreakDancer detected the most deletions, and cn.mops detected the most duplications. The CNVnator showed the highest precision and recall for both deletions and duplications. In real and simulated WGBS data, the ability of CNVnator to detect CNVs was likely to overtake that in the whole genome sequencing data. Additionally, DELLY and BreakDancer displayed the lowest peak of memory usage and the lest CPU runtime, while CNVnator expressed the highest peak of memory usage and the most CPU runtime. Taken together, CNVnator and cn.mops showed the excellent performances of CNV detections with WGBS data. These results suggested that it was feasible to detect CNVs using WGBS data, and provided the useful information to further investigate both CNVs and DNA methylation using WGBS data alone.
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Variações do Número de Cópias de DNA , Genoma Humano , Humanos , Sequenciamento Completo do GenomaRESUMO
Compared with mechanism-based modeling methods, data-driven modeling based on big data has become a popular research field in recent years because of its applicability. However, it is not always better to have more data when building a forecasting model in practical areas. Due to the noise and conflict, redundancy, and inconsistency of big time-series data, the forecasting accuracy may reduce on the contrary. This paper proposes a deep network by selecting and understanding data to improve performance. Firstly, a data self-screening layer (DSSL) with a maximal information distance coefficient (MIDC) is designed to filter input data with high correlation and low redundancy; then, a variational Bayesian gated recurrent unit (VBGRU) is used to improve the anti-noise ability and robustness of the model. Beijing's air quality and meteorological data are conducted in a verification experiment of 24 h PM2.5 concentration forecasting, proving that the proposed model is superior to other models in accuracy.
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BACKGROUND: In mammals, the ovary is the essential system of female reproduction for the onset of puberty, and the abnormal puberty has negative outcomes on health. CircRNA is a non-coding RNA produced by non-canonical alternative splicing (AS). Several studies have reported that circRNA is involved in the gene regulation and plays an important role in some human diseases. However, the contribution of circRNA has received little known within the onset of puberty in ovary. RESULTS: Here, the profiles of ovarian circRNAs across pre-, in- and post-pubertal stages were established by RNA-sEq. In total, 972 circRNAs were identified, including 631 stage-specific circRNAs and 8 tissue-specific circRNAs. The biological functions of parental genes of circRNAs were enriched in steroid biosynthesis, autophagy-animal, MAPK signaling pathway, progesterone-mediated oocyte maturation and ras signaling pathway. Moreover, 5 circRNAs derived from 4 puberty-related genes (ESR1, JAK2, NF1 and ARNT) were found in this study. The A3SS events were the most alternative splicing, but IR events were likely to be arose in post-pubertal ovaries. Besides, the circRNA-miRNA-gene networks were explored for 10 differentially expressed circRNAs. Furthermore, the head-to-tail exon as well as the expressions of 10 circRNAs were validated by the divergent RT-qPCR and sanger sequencing. CONCLUSIONS: In summary, the profiles of ovarian circRNAs were provided during pubertal transition in gilts, and these results provided useful information for the investigation on the onset of puberty at the ovarian-circRNAs-level in mammals.
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MicroRNAs , Ovário , RNA Circular , Maturidade Sexual , Animais , Feminino , Redes Reguladoras de Genes , RNA/genética , Suínos/genéticaRESUMO
OBJECTIVE: To investigate the effect of Linshu Decoction (LSD) combined with levofloxacin in the treatment of lower urinary tract symptoms in patients with type â ¢A prostatitis. METHODS: We randomly divided 124 type â ¢A prostatitis patients with lower urinary tract symptoms into an experimental and a control group, the former treated orally with LSD (1 dose bid) combined with levofloxacin tablets (0.1 g bid), and the latter with levofloxacin tablets only (0.1g bid). Before and after 4 weeks of medication, we obtained the NIH-CPSI, Traditional Chinese Medicine symptoms (TCM) scores, white blood cell (WBC) count in EPS and the results of uroflowmetry from the patients and compared them between the two groups. RESULTS: Finally 115 of the patients were included in this study. After 4 weeks of treatment, the patients of the experimental group, compared with the controls, showed significantly decreased NIH-CPSI (14.57 ± 3.87 vs 20.12 ± 3.45, P < 0.05), TCM scores (6.35 ± 1.27 vs 10.72 ± 1.72, P < 0.05) and WBC count in EPS (ï¼»7.35 ± 4.52ï¼½ vs ï¼»9.87 ± 5.87ï¼½ n/HP, P < 0.05). In comparison with baseline, the maximum urinary flow rate (Qmax) and average urinary flow rate (Qave) were increased in both of the two groups after medication, with statistically significant difference only in the experimental group (P < 0.05). CONCLUSIONS: Linshu Decoction combined with levofloxacin is more effective than levofloxacin alone in the treatment of lower urinary tract symptoms in patients with type â ¢A prostatitis.
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Sintomas do Trato Urinário Inferior , Prostatite , Doença Crônica , Humanos , Levofloxacino/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Masculino , Medicina Tradicional Chinesa , Prostatite/tratamento farmacológicoRESUMO
Premature ejaculation (PE) is a most common type of ejaculatory dysfunction, which has significant adverse effects on the life quality of the patients and their partners. Medication is currently the first choice for PE and psycho-behavior therapy is sometimes used as an adjuvant means. It is reported in a number of studies that medication alone or combined with psycho-behavior therapy has a great short-term efficacy and a very low risk of side effects. Conservative therapies for PE, however, have some obvious disadvantages such as easy recurrence after drug withdrawal, ineffectiveness in some cases, and so on. Thus, clinicians in China and abroad have developed and tried various surgical methods for the treatment of PE, most of which are reportedly safe and effective. However, International Society for Sexual Medicine guidelines for the diagnosis and treatment of PE recommended against surgical methods because of possible permanent loss of sexual function and insufficient reliable data, though without support from evidence or relevant literature. Although controversial, surgical treatment remains an effective and feasible strategy for refractory PE that does not respond to any conservative therapies. This review summarizes a variety of surgical techniques for PE, along with their basic principles, indications, effects and safety.
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Ejaculação Precoce/cirurgia , Terapia Comportamental , China , Tratamento Conservador , Ejaculação , Humanos , Masculino , Ejaculação Precoce/tratamento farmacológico , Qualidade de Vida , Recidiva , Parceiros SexuaisRESUMO
BACKGROUND: Hyperperfusion-induced cerebral hemorrhage (HICH) is a rare but severe complication in patients with carotid stenosis undergoing stent placement for which predictive models are lacking. Our objective was to develop a nomogram to predict such risk. METHODS: We included a total of 1226 patients with carotid stenosis who underwent stenting between June 2015 and December 2022 from three medical centers, divided into a development cohort of 883 patients and a validation cohort of 343 patients. The model used LASSO regression for feature optimization and multivariable logistic regression to develop the predictive model. Model accuracy was assessed via the receiver operating characteristic curve, with further evaluation of calibration and clinical utility through calibration curves and decision curve analysis (DCA). The model underwent internal validation using bootstrapping and external validation with the validation cohort. RESULTS: Older age (OR 1.07, p=0.005), higher degrees of carotid stenosis (OR 1.07, p=0.006), poor collateral circulation (OR 6.26, p<0.001), elevated preoperative triglyceride levels (OR 1.27, p=0.041) and neutrophil counts (OR 1.36, p<0.001) were identified as independent risk factors for HICH during hospitalization. The nomogram constructed based on these predictive factors demonstrated an area under the curve (AUC) of 0.817. The AUCs for internal and external validation were 0.809 and 0.783, respectively. Calibration curves indicated good model fit, and DCA confirmed substantial clinical net benefit in both cohorts. CONCLUSION: We developed and validated a nomogram to predict HICH in patients with carotid stenosis post-stenting, facilitating early identification and preventive intervention in high-risk individuals.
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BACKGROUND AND OBJECTIVES: Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes. METHODS: We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes. RESULTS: Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001). CONCLUSION: Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.
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Enhancers and the enhancer RNAs (eRNAs) have been strongly implicated in regulations of transcriptions. Based the multi-omics data (ATAC-seq, ChIP-seq and RNA-seq) from public databases, Pig-eRNAdb is a dataset that comprehensively integrates enhancers and eRNAs for pigs using the machine learning strategy, which incorporates 82,399 enhancers and 37,803 eRNAs from 607 samples across 15 tissues of pigs. This user-friendly dataset covers a comprehensive depth of enhancers and eRNAs annotation for pigs. The coordinates of enhancers and the expression patterns of eRNAs are downloadable. Besides, thousands of regulators on eRNAs, the target genes of eRNAs, the tissue-specific eRNAs, and the housekeeping eRNAs are also accessible as well as the sequence similarity of eRNAs with humans. Moreover, the tissue-specific eRNA-trait associations encompass 652 traits are also provided. It will crucially facilitate investigations on enhancers and eRNAs with Pig-eRNAdb as a reference dataset in pigs.
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Elementos Facilitadores Genéticos , Transcrição Gênica , Animais , Regiões Promotoras Genéticas , RNA/genética , SuínosRESUMO
BACKGROUND AND OBJECTIVES: Understanding post-treatment hemodynamic alterations and their association with the patency of covered branch arteries is limited. This study aims to identify hemodynamic changes after flow diverter stenting and investigate their correlation with the patency status of covered branch arteries. METHODS: All patients treated with pipeline embolization device for anterior cerebral artery aneurysms at our center between 2016 and 2020 were screened for inclusion. Quantitative digital subtraction angiography was used to analyze changes in hemodynamic parameters pre- and post-stenting. The patency status of covered branch arteries after stenting was categorized as either patent or flow impairment (defined as artery stenosis or occlusion). RESULTS: A total of 71 patients, encompassing 89 covered branch arteries, were enrolled. Flow impairment was observed in 11.2% (10/89) of the branches. The mean transit time and full width at half maximum (FWHM) in covered branches were significantly prolonged post-stenting (P = .004 and .023, respectively). Flow-impaired branch arteries exhibited hemodynamic shifts contrary to those in patent branch arteries. Specifically, flow-impaired branches showed marked reductions in time to peak, FWHM, and mean transit time (decreases of 32.8%, 32.6%, and 29%, respectively; P = .006, .002, and .002, respectively). Further multivariate analysis revealed that reductions in FWHM in the branches (odds ratio = 0.97, 95% CI: 0.95-0.99, P = .007) and smoking (odds ratio = 14.5, 95% CI: 1.39-151.76, P = .026) were independent predictors of flow impairment of covered branches. CONCLUSION: Pipeline embolization device stenting can cause a reduction in blood flow in branch arteries. Compared with patent branches, flow-impaired branches exhibit an increase in blood flow velocity after stenting. Smoking and ΔFWHM in the covered branches indicate flow impairment.
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BACKGROUND: Detecting and segmenting intracranial aneurysms (IAs) from angiographic images is a laborious task. OBJECTIVE: To evaluates a novel deep-learning algorithm, named vessel attention (VA)-Unet, for the efficient detection and segmentation of IAs. METHODS: This retrospective study was conducted using head CT angiography (CTA) examinations depicting IAs from two hospitals in China between 2010 and 2021. Training included cases with subarachnoid hemorrhage (SAH) and arterial stenosis, common accompanying vascular abnormalities. Testing was performed in cohorts with reference-standard digital subtraction angiography (cohort 1), with SAH (cohort 2), acquired outside the time interval of training data (cohort 3), and an external dataset (cohort 4). The algorithm's performance was evaluated using sensitivity, recall, false positives per case (FPs/case), and Dice coefficient, with manual segmentation as the reference standard. RESULTS: The study included 3190 CTA scans with 4124 IAs. Sensitivity, recall, and FPs/case for detection of IAs were, respectively, 98.58%, 96.17%, and 2.08 in cohort 1; 95.00%, 88.8%, and 3.62 in cohort 2; 96.00%, 93.77%, and 2.60 in cohort 3; and, 96.17%, 94.05%, and 3.60 in external cohort 4. The segmentation accuracy, as measured by the Dice coefficient, was 0.78, 0.71, 0.71, and 0.66 for cohorts 1-4, respectively. VA-Unet detection recall and FPs/case and segmentation accuracy were affected by several clinical factors, including aneurysm size, bifurcation aneurysms, and the presence of arterial stenosis and SAH. CONCLUSIONS: VA-Unet accurately detected and segmented IAs in head CTA comparably to expert interpretation. The proposed algorithm has significant potential to assist radiologists in efficiently detecting and segmenting IAs from CTA images.
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Background: Stent placement can be an effective treatment for patients with symptomatic intracranial stenosis (sICAS) and hemodynamic impairment (HI). However, the association between lesion length and the risk of recurrent cerebral ischemia (RCI) after stenting remains controversial. Exploring this association can help predict patients at higher risk for RCI and develop individualized follow-up schedules. Method: In this study, we provided a post-hoc analysis of a prospective, multicenter registry study on stenting for sICAS with HI in China. Demographics, vascular risk factors, clinical variables, lesions, and procedure-specific variables were recorded. RCI includes ischemic stroke and transient ischemic attack (TIA), from month 1 after stenting to the end of the follow-up period. Smoothing curve fitting and segmented Cox regression analysis were used to analyze the threshold effect between lesion length and RCI in the overall group and subgroups of the stent type. Results: The non-linear relationship between lesion length and RCI was observed in the overall population and subgroups; however, the non-linear relationship differed by subgroup of stent type. In the balloon-expandable stent (BES) subgroup, the risk of RCI increased 2.17-fold and 3.17-fold for each 1-mm increase in the lesion length when the lesion length was <7.70 mm and >9.00 mm, respectively. In the self-expanding stent (SES) subgroup, the risk of RCI increased 1.83-fold for each 1-mm increase in the lesion length when the length was <9.00 mm. Nevertheless, the risk of RCI did not increase with the length when the lesion length was >9.00mm. Conclusion: A non-linear relationship exists between lesion length and RCI after stenting for sICAS with HI. The lesion length increases the overall risk of RCI for BES and for SES when the length was <9.00 mm, while no significant relationship was found when the length was >9.00 mm for SES.
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Background: The risk of perioperative stroke and the rate of occlusion of long-term aneurysms in the treatment of unruptured aneurysms with flow diverters (FDs) are affected by stent apposition. Optical coherence tomography (OCT) may be an optional technique in evaluating apposition. Purpose: To explore the feasibility of the OCT imaging technique in evaluating stent apposition in the clinical application of the FD for unruptured aneurysms. Methods: OCT and Vaso CT were used in patients with indications for surgery to treat unruptured aneurysms with the FDs, to evaluate the apposition of the FDs after fully released, and to analyze OCT images for FDs apposition and compare with corresponding Vaso CT images. Results: A total of four patients were enrolled, and OCT found malapposition after FDs placement in all four patients, and the maximum gap between the stent and vascular wall ranged from 0.68 to 1.95 mm and the length of malapposition ranged from 1.80 to 7.40 mm. However, Vaso CT found malapposition only in two of the four patients and missed malapposition near aneurysm in all three patients treated by the FD combined with coiling and could not accurately evaluate the maximum gap and the length of the malapposition. Conclusion: The optical coherence tomography technique is a possible approach to evaluate apposition after the treatment of unruptured aneurysms by the FDs.
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Pigs have become an ideal model system for human disease research and development and an important farm animal that provides a valuable source of nutrition. To profile the all-sided gene expression and their biological functions across multiple tissues, we conducted a comprehensive analysis of gene expression on a large scale around the side of housekeeping genes (HKGs), tissue specific genes (TSGs), and the co-expressed genes in 14 various tissues. In this study, we identified 2351 HKGs and 3018 TSGs across tissues, among which 4 HKGs (COX1, UBB, OAZ1/NPFF) exhibited low variation and high expression levels, and 31 particular TSGs (e.g., PDC, FKBP6, STAT2, and COL1A1) were exclusively expressed in several tissues, including endocrine brain, ovaries, livers, backfat, jejunum, kidneys, lungs, and longissimus dorsi muscles. We also obtained 17 modules with 230 hub genes (HUBGs) by weighted gene co-expression network analysis. On the other hand, HKGs functions were enriched in the signaling pathways of the ribosome, spliceosome, thermogenesis, oxidative phosphorylation, and nucleocytoplasmic transport, which have been highly suggested to involve in the basic biological tissue activities. While TSGs were highly enriched in the signaling pathways that were involved in specific physiological processes, such as the ovarian steroidogenesis pathway in ovaries and the renin-angiotensin system pathway in kidneys. Collectively, these stable, specifical, and co-expressed genes provided useful information for the investigation of the molecular mechanism for an understanding of the genetic and biological processes of complex traits in pigs.
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Whole genome bisulfite sequencing (WGBS) is an essential technique for methylome studies. Although a series of tools have been developed to overcome the mapping challenges caused by bisulfite treatment, the latest available tools have not been evaluated on the performance of reads mapping as well as on biological insights in multiple mammals. Herein, based on the real and simulated WGBS data of 14.77 billion reads, we undertook 936 mappings to benchmark and evaluate 14 wildly utilized alignment algorithms from reads mapping to biological interpretation in humans, cattle and pigs: Bwa-meth, BSBolt, BSMAP, Walt, Abismal, Batmeth2, Hisat_3n, Hisat_3n_repeat, Bismark-bwt2-e2e, Bismark-his2, BSSeeker2-bwt, BSSeeker2-soap2, BSSeeker2-bwt2-e2e and BSSeeker2-bwt2-local. Specifically, Bwa-meth, BSBolt, BSMAP, Bismark-bwt2-e2e and Walt exhibited higher uniquely mapped reads, mapped precision, recall and F1 score than other nine alignment algorithms, and the influences of distinct alignment algorithms on the methylomes varied considerably at the numbers and methylation levels of CpG sites, the calling of differentially methylated CpGs (DMCs) and regions (DMRs). Moreover, we reported that BSMAP showed the highest accuracy at the detection of CpG coordinates and methylation levels, the calling of DMCs, DMRs, DMR-related genes and signaling pathways. These results suggested that careful selection of algorithms to profile the genome-wide DNA methylation is required, and our works provided investigators with useful information on the choice of alignment algorithms to effectively improve the DNA methylation detection accuracy in mammals.
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Objective: Stent placement is a feasible approach worldwidely for patients with symptomatic intracranial artery stenosis (sICAS) and hemodynamic impairment (HI) who are at high risk of recurrent stroke after medical treatment. Exploration of factors associated with poor outcomes after stent placement could help develop better individualized therapeutic strategies. Methods: This study conducted a post-hoc analysis of a prospective, multicenter registry study of stent use for sICAS with HI in China. Patient and clinical demographics, and stenotic lesion images were analyzed using univariate and multivariate Cox regression to the time until any endpoints or the end of the follow-up period. The short-term endpoint included any transient ischemic attack (TIA), stroke, or death within 1 month after stent placement. The long-term endpoints included the short-term endpoints and any TIA or stroke in the region of the affected artery that occurred more than 1 month after stent placement. Results: Two hundred and ninety two patients were included, with 13 short-term and 39 long-term endpoints. Multivariate Cox regression analysis revealed that lesions at the arterial origin or bifurcation (Hazard Ratio (HR) = 7.52; 95% CI, 1.89-29.82; p = 0.004) were significantly associated with higher short-term risk. Baseline renal insufficiency reduced the risk (HR = 0.08; 95% CI: 0.01-0.68; p = 0.021). Factors significantly associated with higher long-term risk included irregular or ulcerated plaques at the lesion (HR = 2.15; 95% CI: 1.07-4.33; p = 0.031). Subgroup analyses indicated that higher risk occurred in the older age group (age>59 years, HR = 3.73, 95% CI: 1.27-10.97, p = 0.017), and not in the younger group (age≤59 years, HR = 1.12, 95% CI: 0.42-3.03, p = 0.822). Conclusion: Irregular or ulcerated plaques in older patients and lesions at the arterial opening or bifurcation were more likely to result in adverse endpoints for stent placement during long or short -term follow-up. Investigation of these factors might facilitate the development of individualized therapeutic strategies for this population. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier: NCT01968122.
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OBJECTIVE: The objective of this study was to assess the safety, feasibility, and outcomes of endovascular recanalization for symptomatic intracranial internal carotid and middle cerebral artery occlusion lasting longer than 72 h. METHODS: Thirty-nine consecutive patients with symptomatic occlusion of the anterior circulation and failure of medical therapy underwent endovascular recanalization and were included in this retrospective study. Patient characteristics, atherosclerotic risk factors, successful recanalization rates, and angiographic data were collected. RESULTS: Recanalization was successful in 37 cases (94.9%). The average residual stenosis immediately after intervention was 11.6 ± 4.3%. The patients who underwent balloon angioplasty alone had similar residual stenosis to those who also underwent stent placement (15.6 ± 7.3% vs. 9.0 ± 6.4%, P = 0.184). Intra- and perioperative complications occurred in three cases (7.69%). One patient (2.7%) developed severe in-stent restenosis with transient ischemic attack symptoms at 1-year follow-up. CONCLUSIONS: Endovascular recanalization is feasible for symptomatic occlusion of the anterior circulation lasting longer than 72 h. Recanalization provides a higher success rate when performed within 6 months of the qualifying event.
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The disorders of puberty have shown negative outcomes on health of mammals, and the hypothalamus is thought to be the main regulator of puberty by releasing GnRH. Many studies show that the circular RNAs (circRNAs) might be implicated in the timing of puberty in mammals. However, the circRNAs in the hypothalamus of gilts have not been explored. To profile the changes and biological functions of circRNAs in the hypothalamus during the onset of puberty, RNA-seq was utilized to establish pre-, in-, and post-pubertal hypothalamic circRNAs profiles. In this study, the functions of hypothalamic circRNAs were enriched in the signaling pathway of neurotrophin, progesterone-mediated oocyte maturation, oocyte meiosis, insulin, ErbB, and mTOR, which have been highly suggested to be involved in the timing of puberty. Furthermore, 53 circRNAs were identified to be putative hypothalamus-specific expressed circRNAs, and some of them were exclusively expressed in the one of three pubertal stages. Moreover, 22 differentially expressed circRNAs were identified and chosen to construct the circRNA-miRNA-gene network. Moreover, 10 circRNAs were found to be driven by six puberty-related genes (ESR1, NF1, APP, ENPP2, ARNT, and DICER1). Subsequently, the expression changes of several circRNAs were confirmed by RT-qPCR. Collectively, the preliminary results of hypothalamic circRNAs provided useful information for the investigation of the molecular mechanism for the timing of puberty in gilts.