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Purpose: To analyze the radiological features of the lacrimal gland (LG) and extraocular muscle (EOM) in thyroid eye disease (TED) patients with severe subjective dry eye disease (DED) using magnetic resonance imaging (MRI) measurements. Methods: In this cross-sectional study, mechanical ocular exposure, dry eye assessment and MRI data were collected. Patients were classified into non-severe subjective DED group with ocular surface disease index (OSDI) < 33 and severe subjective DED group with OSDI ≥ 33. Linear regression model was applied for comparing the OSDI < 33 and OSDI ≥ 33 group in TED patients. The predictive performance of MRI parameters and models was assessed by receiver operating characteristic curve (ROC) analysis. Results: Consecutive 88 TED patients (176 eyes) were included in this study. In the OSDI < 33 group, 52 TED patients (104 eyes) with a mean clinical activity score (CAS) of 0.63 ± 0.75. In the OSDI ≥ 33 group, there are 36 TED patients (72 eyes), with a mean CAS of 1.50 ± 1.54. The age and sex of the patients were matched between the two groups. The OSDI ≥ 33 group had shorter tear break-up time, larger levator palpebrae superioris / superior rectus (LPS/SR), inferior rectus and lateral rectus, smaller LG, more inflammatory LPS/SR and inferior rectus than OSDI < 33 DED group (P < 0.05). In the linear regression analysis, compare to the OSDI < 33 DED group, the OSDI ≥ 33 group had larger medial rectus cross-sectional area (β = 0.06, 95%CI: (0.02, 0.10), P = 0.008), larger inferior rectus cross-sectional area (β = 0.06, 95%CI: (0.00, 0.12), P = 0.048), smaller LG cross-sectional area (β = -0.14, 95%CI: (-0.25, -0.04), P = 0.008). In the ROC analysis, the area under curve of medial rectus, inferior rectus, LG, and combined model are 0.625, 0.640, 0.661 and 0.716, respectively. Conclusion: Multiparametric MRI parameters of the LG and EOM in TED patients with severe subjective DED were significantly altered. Novel models combining the cross-sectional area of LG, medial rectus and inferior rectus showed good predictive performance in TED patients with severe subjective DED. [ABSTRACT FROM AUTHOR]

Rhizopus nigricans (R. nigricans), one of the fungi that grows the fastest, is frequently discovered in postharvest fruits, it's the main pathogen of strawberry root rot. Flavonoids in Sedum aizoon L. (FSAL) is a kind of green and safe natural substance extracted from Sedum aizoon L. which has antifungal activity. In this study, the minimum inhibitory concentration (MIC) of FSAL on R. nigricans and cell apoptosis tests were studied to explore the inhibitory effect of FSAL on R. nigricans. The effects of FSAL on mitochondria of R. nigricans were investigated through the changes of mitochondrial permeability transition pore(mPTP), mitochondrial membrane potential(MMP), Ca2+ content, H2O2 content, cytochrome c (Cyt c) content, the related enzyme activity and related genes of mitochondria. The results showed that the MIC of FSAL on R. nigricans was 1.800 mg/mL, with the addition of FSAL (1.800 mg/mL), the mPTP openness of R. nigricans increased and the MMP reduced. Resulting in an increase in Ca2+ content, accumulation of H2O2 content and decrease of Cyt c content, the activity of related enzymes was inhibited and related genes were up-regulated (VDAC1, ANT) or down-regulated (SDHA, NOX2). This suggests that FSAL may achieve the inhibitory effect of fungi by damaging mitochondria, thereby realizing the postharvest freshness preservation of strawberries. This lays the foundation for the development of a new plant-derived antimicrobial agent. [ABSTRACT FROM AUTHOR]

The occurrence of gray mold is the main cause of rot and spoilage in grapes, and Botrytis cinerea is the main causative agent of gray mold. The aim of this study is to clarify the inhibitory effect of flavonoids from Sedum aizoon L. (FSAL) on gray mold of grapes and to provide some basis for the development of new natural plant-derived antifungal agents. The effect of FSAL on the disease resistance of grapes was investigated by measuring the disease incidence and lesion diameter. The effect of FSAL on fruit quality was studied by measuring pondus hydrogenii (pH), total soluble solid (TSS), ascorbic acid (AA) and soluble sugar content. The activities of catalase (CAT), peroxidase (POD), phenylalanine ammonia lyase (PAL), and superoxide dismutase (SOD) were used to explore the effect of FSAL on the antioxidant capacities in grapes. The effects of FSAL on the ethylene synthesis in mitogen-activated protein kinase (MAPK) signaling pathway in grapes were investigated by measuring the levels of reactive oxygen species (ROS) and the relative expression of VvACS1, VvACO1, VvACO2, and VvACO3 genes. The results showed that FSAL treatment reduced disease incidence and lesion diameter, increased AA content in fruit and thus maintained fruit quality. FSAL treatment significantly increased CAT, POD, PAL, and SOD activities in fruit, and reduced the relative expression of the genes. In conclusion, FSAL has a certain inhibitory effect on gray mold while not affecting grape quality, and delays the ripening and aging of fruit. [ABSTRACT FROM AUTHOR]

In recent decades, magnetic nanomaterials with fast separation and recyclable performance have raised great interest for broad applications in catalysis, protein separation and immunodiagnostics. In this paper, Fe3O4 nanoparticles with a size of (350 ± 50) nm were produced by the solvothermal method. Then, the nanoparticles were coated with a shell made of 3-aminophenol-formaldehyde (APF) resin to prevent agglomeration. The reaction was very rapid, and core–shell Fe3O4@APF nanospheres were produced by polycondensation within 10 min. Besides, the thickness of the APF shell could be easily adjusted in the range of 10–200 nm by controlling the reaction time and the concentration of 3-aminophenol and formaldehyde. In particular, the APF layer could also act as an effective carrier and reducing agent to capture hundreds of well-dispersed Ag nanoparticles for the abundant hydroxyl groups, obtaining sesame-ball-like Fe3O4@APF@Ag nanocomposites. The structure of sesame-ball can prevent silver nanoparticles from agglomerating, and Fe3O4 core could provide strong magnetism. The magnetic Fe3O4@APF@Ag nanomaterials could catalyze the reduction of organic dyes (4-NP, MB and RhB), and the catalyst possessed high activity, with the conversion of dyes remaining above 90% within 3 min after 7 cycles. [ABSTRACT FROM AUTHOR]

Dysregulation of Th17 cell differentiation and pathogenicity contributes to multiple autoimmune and inflammatory diseases. Previously growth hormone releasing hormone receptor (GHRH-R) deficient mice have been reported to be less susceptible to the induction of experimental autoimmune encephalomyelitis. Here, we show GHRH-R is an important regulator of Th17 cell differentiation in Th17 cell-mediated ocular and neural inflammation. We find that GHRH-R is not expressed in naïve CD4+ T cells, while its expression is induced throughout Th17 cell differentiation in vitro. Mechanistically, GHRH-R activates the JAK-STAT3 pathway, increases the phosphorylation of STAT3, enhances both non-pathogenic and pathogenic Th17 cell differentiation and promotes the gene expression signatures of pathogenic Th17 cells. Enhancing this signaling by GHRH agonist promotes, while inhibiting this signaling by GHRH antagonist or GHRH-R deficiency reduces, Th17 cell differentiation in vitro and Th17 cell-mediated ocular and neural inflammation in vivo. Thus, GHRH-R signaling functions as a critical factor that regulates Th17 cell differentiation and Th17 cell-mediated autoimmune ocular and neural inflammation. Endocrine factors have been shown to alter functions of pathogenic Th17 cells that are involved in autoimmunity. Here the authors study the influence of growth hormone releasing hormone receptor and show that this receptor is found on Th17 cells and promotes ocular autoimmunity. [ABSTRACT FROM AUTHOR]

Pseudomonas fragi (P. fragi) is one of the main categories of bacteria responsible for the spoilage of chilled meat. In the processing and preservation of chilled meat, it is easy to form biofilms on the meat, leading to the development of slime on the meat, which becomes a major quality defect. Flavonoids, as one of the critical components of secondary plant metabolites, are receiving increasing attention for their antibacterial activity. Flavonoids in Sedum aizoon L. (FSAL), relying on its prominent antibacterial activity, are of research importance in food preservation and other applications. This article aims to investigate the effect of FSAL on the biofilm formation of P. fragi, to better apply FSAL to the processing and preservation of meat products. The disruption of cellular structure and aggregation properties by FSAL was demonstrated by the observation of the cellular state within the biofilm. The amount of biofilm formation was determined by crystal violet staining, and the content of polysaccharides and proteins in the extracellular wrapped material was determined. It was shown that the experimental concentrations of FSAL (1.0 MIC) was able to inhibit biofilm formation and reduce the main components in the extracellular secretion. The swimming motility assay and the downregulation of flagellin-related genes confirmed that FSAL reduced cell motility and adhesion. The downregulation of cell division genes and the lowering of bacterial metabolic activity suggested that FSAL could hinder bacterial growth and reproduction within P. fragi biofilms. Key points: • FSAL inhibited the activity of Pseudomonas fragi in the dominant meat strain • The absence of EPS components affected the formation of P. fragi biofilms • P. fragi has reduced adhesion capacity due to impaired flagellin function [ABSTRACT FROM AUTHOR]

In this paper, the authors first discuss the characterization of Herz Triebel–Lizorkin spaces with variable exponent via two families of operators. By this characterization, the authors prove that the Lipschitz commutators of sublinear operators is bounded from Herz spaces with variable exponent to Herz Triebel–Lizorkin spaces with variable exponent. As applications, the corresponding boundedness estimates for the commutators of maximal operator, Riesz potential operator and Calderón–Zygmund operator are established. [ABSTRACT FROM AUTHOR]

The Golgi apparatus is one of the important organelles, where the final processing and packaging of cellular secretions (such as proteins) are completed. The disorder of Golgi apparatus structure and function will induce many diseases. Therefore, monitoring the morphological structure of Golgi apparatus is crucial for the diagnosis and treatment of relevant diseases. In order to achieve Golgi apparatus-targeting imaging, the strategy of targeting unit inheritance was adopted and carbon dots (CDs) with Golgi apparatus-targeting ability were synthesized by one-step hydrothermal method with L-ascorbic acid with high reactivity and reducibility as the carbon source and L-cysteine as the targeting unit. CDs have a certain amount of cysteine residues on their surface, and have excitation dependence, satisfactory fluorescence and cysteine residues stability and low toxicity. As an imaging agent, CDs can be used for targeting imaging of Golgi apparatus. [ABSTRACT FROM AUTHOR]

Botrytis cinerea is a highly destructive and widespread phytopathogen in fruits. The widespread use of chemical antifungal agents on fruits has aided in disease control while their long-term use has resulted in the emergence of resistant fungal strains. Flavonoids have a specific antifungal effect. The inhibitory effect and underlying mechanism of flavonoids from Sedum aizoon L. (FSAL) on B. cinerea were determined in this study. The results showed that the minimum inhibitory concentration of FSAL against B. cinerea was 1.500 mg/mL. FSAL treatment caused leakage of macromolecules such as nucleic acids, led to accumulation of malondialdehyde and relative oxygen species, and disrupted the ultrastructure of B. cinerea. The transcriptome results indicated that compared with the control group, there were 782 and 1330 genes identified as being substantially upregulated and downregulated, respectively, in the FSAL-treated group. The identified genes and metabolites were mostly involved in redox processes and glycerolipid and amino acid metabolism pathways. FSAL offer a promising choice for food prevention and safety. Key points: • FSAL negatively affects the glycerolipid metabolism of B. cinerea • FSAL minimum inhibitory concentration against B. cinerea was 1.500 mg/mL • FSAL could be utilized as a new prevention strategy for gray mold in fruits [ABSTRACT FROM AUTHOR]

Uniform design is one of the most frequently used designs of experiment, and all factors are usually regarded as equally important in the existing literature of uniform design. If some prior information of certain factors is known, the potential importance of factors should be distinguished. In this paper, by assigning different weights to factors with different importance, the weighted wrap-around L 2 -discrepancy is proposed to measure the uniformity of design when some prior information of certain factors are known. The properties of weighted wrap-around L 2 -discrepancy are explored. Accordingly, the weighted generalized wordlength pattern is proposed to describe the aberration of these kinds of designs. The relationship between the weighted wrap-around L 2 -discrepancy and weighted generalized wordlength pattern is built, and a lower bound of weighted wrap-around L 2 -discrepancy is obtained. Numerical results show that both weighted wrap-around L 2 -discrepancy and weighted generalized wordlength pattern are precisely to capture the difference of importance among the columns of design. [ABSTRACT FROM AUTHOR]

Effect of fresh-cut procedure on the accumulation of GABA in carrots via γ-aminobutyric acid (GABA) shunt and polyamines degradation pathway was investigated. Results showed that fresh-cut processing enhanced glutamate decarboxylase (GAD) activity and expression levels of DcGAD1 and DcGAD2, while reduced GABA transaminase (GABA-T) activity and DcGABA-T1 expression level, which induced the more glutamate (Glu) conversion to GABA. Polyamines (PAs) in shredded carrots were significantly lower than the whole, due to the elevated activities of diamine oxidase (DAO), polyamine oxidase (PAO) and aminoaldehyde dehydrogenase (AMADH) and DcPAO expression level, which indicated that the polyamines degradation pathway was activated and more PAs were converted to GABA. These results suggested that fresh-cut procedure can induce the accumulation of GABA through activating GABA shunt and polyamines degradation pathway. Besides, fresh-cut processing treatment did not have much adverse effect on the organoleptic quality of carrots. [ABSTRACT FROM AUTHOR]

High fluorescence quantum yield (QY), excellent fluorescence stability, and low toxicity are essential for a good cellular imaging fluorescent probe. Green-emissive carbon quantum dots (CQDs) with many advantages, such as unique fluorescence properties, anti-photobleaching, low toxicity, fine biocompatibility and high penetration depth in tissues, have been considered as a potential candidate in cell imaging fluorescent probes. Herein, N, S-codoped green-emissive CQDs (QY = 64.03%) were synthesized by the one-step hydrothermal method, with m-phenylenediamine as the carbon and nitrogen source, and L-cysteine as the nitrogen and sulfur dopant, under the optimum condition of 200 °C reaction for 2 h. Their luminescence was found to originate from the surface state. In light of the satisfactory photobleaching resistance and the low cytotoxicity, CQDs were used as a cell imaging probe for HeLa cell imaging. The results clearly indicate that cells can be labeled with CQDs, which can not only enter the cytoplasm, but also enter the nucleus through the nuclear pore, showing their broad application prospect in the field of cell imaging. [ABSTRACT FROM AUTHOR]

The transcription regulatory network inside a eukaryotic cell is defined by the combinatorial actions of transcription factors (TFs). However, TF binding studies in plants are too few in number to produce a general picture of this complex network. In this study, we use large-scale ChIP-seq to reconstruct it in the maize leaf, and train machine-learning models to predict TF binding and co-localization. The resulting network covers 77% of the expressed genes, and shows a scale-free topology and functional modularity like a real-world network. TF binding sequence preferences are conserved within family, while co-binding could be key for their binding specificity. Cross-species comparison shows that core network nodes at the top of the transmission of information being more conserved than those at the bottom. This study reveals the complex and redundant nature of the plant transcription regulatory network, and sheds light on its architecture, organizing principle and evolutionary trajectory. Transcriptional factors (TFs) bind in a combinatorial fashion to specify the on-and-off states of genes in a complex and redundant regulatory network. Here, the authors construct the transcription regulatory network in maize leaf using 104 TFs ChIP-seq data and train machine learning models to predict TF binding and colocalization. [ABSTRACT FROM AUTHOR]

Flavonoids from Sedum aizoon L. (FSAL) possess prominent antibacterial activity against Shewanella putrefaciens isolated from sea food. In the current study, the involved molecular mechanisms were investigated using transcriptome analyses combined with bioinformatics analysis in vitro for the first time. Results showed that treatment of FSAL (1.0 MIC) damaged the permeability and integrity of cell membrane and induced 721 differentially expressed genes (DEGs) in tested bacteria at transcriptional levels, including 107 DEGs were up-regulated and 614 DEGs were down-regulated. In addition, the RNA-Seq analysis revealed that the majority of DEGs mainly involved in pathways of lipopolysaccharide biosynthesis, glycerophospholipid metabolism, biosynthesis of amino acids, purine metabolism, ABC transporters and response to stimulus. In summary, the integrated results indicated that the intervention of FSAL induced destruction of cell wall and membrane, disorder of the metabolic process and redox balance, and damage of nucleic acids in S. putrefaciens, at last resulted in the death of cells. This study provided new insights into the anti- S. putrefaciens molecular mechanism underlying the treatment of FSAL, which may be served as the basis guide for identifying potential antimicrobial targets and application of FSAL in food safety. [ABSTRACT FROM AUTHOR]

Despite their widespread applications, single-cell RNA-sequencing (scRNA-seq) experiments are still plagued by batch effects and dropout events. Although the completely randomized experimental design has frequently been advocated to control for batch effects, it is rarely implemented in real applications due to time and budget constraints. Here, we mathematically prove that under two more flexible and realistic experimental designs—the reference panel and the chain-type designs—true biological variability can also be separated from batch effects. We develop Batch effects correction with Unknown Subtypes for scRNA-seq data (BUSseq), which is an interpretable Bayesian hierarchical model that closely follows the data-generating mechanism of scRNA-seq experiments. BUSseq can simultaneously correct batch effects, cluster cell types, impute missing data caused by dropout events, and detect differentially expressed genes without requiring a preliminary normalization step. We demonstrate that BUSseq outperforms existing methods with simulated and real data. It is not clear which designs, other than completely randomized ones, are valid for scRNA-seq experiments so that batch effects can be adjusted. Here the authors show that under flexible reference panel and chain-type designs, biological variability can also be separated from batch effects, at least by BUSseq. [ABSTRACT FROM AUTHOR]

We investigated the effects of at-harvest maturity of 'YuLu' peach fruit on soluble sugar metabolism and their relationship with chilling injury susceptibility. Peaches were sorted into four maturity groups at harvest by IAD (index of the absorbance difference between 670 and 720 nm) then stored at 5 °C for 28 days. Fruit quality parameters, flesh browning index, malondialdehyde (MDA) content, soluble sugar content, gene expression, and enzyme activities associated with sucrose metabolism were measured. The more mature fruit groups had significantly (p < 0.05) lower firmness, higher soluble solid content, a* values of background color, sorbitol and sucrose content at harvest. During the cold storage, the higher flesh browning index in the mature groups (M3 and M4) maybe due to the double stress of senescence and chilling injury because there was concomitant sharp increase in MDA content. However, the most immature at-harvest group (M1) had the significantly (p < 0.05) higher MDA content after 14 days of cold storage, and a flesh browning index significantly (p < 0.05) higher than the M2 group (the next more mature group), late in the storage period. Moreover, the M1 group had lower sucrose content at postharvest and higher activities and transcript levels of sucrose degrading enzymes and lower levels of sucrose synthesis enzymes, which was responsible for the lower sucrose levels than M2 group during storage. It was concluded that the more immature peach fruit with lower sucrose content, have a higher chilling susceptibility than more mature fruit. [ABSTRACT FROM AUTHOR]

Natural products extracted from plants are an alternative method for controlling postharvest citrus blue mold, caused by Penicillium italicum (P. italicum). In this study, RNA sequence analysis was used to investigate the underlying anti-fungal mechanism of flavonoids from Sedum aizoon L. (FSAL) on P. italicum. Significant differences in 3592 genes were observed, including 2507 up-regulated and 1085 down-regulated genes between the FSAL-treated and the control groups. Furthermore, the GO and KEGG analysis results indicated that FSAL inhibited genes related to the integral components of membrane, oxidation–reduction process, mitochondrion, ribosome, and amino acid metabolism. In the presence of FSAL, the cellular constituents, including DNA and RNA were leaked from hyphae of P. italicum. Reactive oxygen species (ROS) production in P. italicum was also determined with a significant concentration-effect under the treatment of FSAL. Thus, we speculate that the inhibitory activity of FSAL on P. italicum is mainly achieved by damaging the structure of the cell membrane and cell wall, disrupting the process of mitochondrial respiratory metabolism, protein biosynthesis, and amino acid metabolism, leading to cell death. The present study provided a global perspective on the molecular mechanism of FSAL on P. italicum through transcriptome analysis, which may help develop a novel plant-derived anti-fungal agent for the blue mold of citrus. [ABSTRACT FROM AUTHOR]

Background: Both ectopia lentis and retinal injury are common results of blunt ocular trauma. Here, we investigated the incidence and characteristics of retinal breaks associated with ectopia lentis caused by blunt ocular trauma. Methods: Patients who underwent pars plana vitrectomy to treat traumatic lens subluxation and dislocation were retrospectively reviewed. The incidence, characteristics, and outcomes of retinal breaks were analyzed. Results: Forty-five eyes from 45 patients were included in the study. Seventeen eyes (37.7%) were complicated by retinal breaks or detachment, but only four (8.9%) were identified pre-operation. Our study revealed that retinal breaks were more frequently located at the superior (72.7%) and peripheral (81.8%) retina. All patients achieved anatomic recovery post-surgery. The eyes with and without retinal breaks did not differ significantly with respect to initial or final visual acuity. The final visual outcomes were independently and significantly associated with visual acuity at presentation (P = 0.001). Conclusions: Retinal breaks occurred in approximately one-third of patients with traumatic ectopia lentis and were difficult to observe pre-operation. Complete ophthalmic evaluation and timely intervention may help achieve favorable outcomes. [ABSTRACT FROM AUTHOR]

Tea tree oil (TTO) and its two characteristic components (terpinen-4-ol and 1,8-cineole) have been shown to inhibit Botrytis cinerea growth. In this study, we conducted a transcriptome analysis to determine the effects of TTO and its characteristic components, alone and in combination, against B. cinerea. Most differentially expressed genes (DEGs) from B. cinerea cells treated with terpinen-4-ol participated in the biosynthesis of secondary metabolites, and the metabolism of amino acids, carbohydrates, and lipids. All treatments containing terpinen-4-ol potentially induced mitochondrial dysfunction and oxidative stress. These were further confirmed by the decreased activities of several enzymes (e.g., succinate dehydrogenase (SDH), malate dehydrogenase (MDH), α-ketoglutarate dehydrogenase (α-KGDH), isocitrate dehydrogenase (ICDH)), the increased activities of certain enzymes (e.g., catalase (CAT), peroxidase (POD), superoxide dismutase (SOD)), and increased content of hydrogen peroxide (H2O2). 1,8-Cineole mainly affected DEGs involved in genetic information processing, resulting in cell death. This study provides insight into the molecular mechanism of B. cinerea inhibition by TTO, and explains the synergistic effect of terpinen-4-ol and 1,8-cineole on B. cinerea. [ABSTRACT FROM AUTHOR]

Peony seed oil has recently been introduced as a high-quality food oil. Because the high price of peony seed oil may tempt unscrupulous merchants to dilute it with cheaper substitutes, a rapid detection method for likely adulterants is required. In this study, the fatty acid composition of peony seed oil and four less expensive edible oils (soybean oil, corn oil, sunflower oil, and rapeseed oil) were measured by gas chromatography mass spectrometry. Peony oil adulterated by other edible oils was assessed using iodine values to estimate the extent of adulteration. Adulteration was also measured using an electronic nose (E-nose) combined with principal component analysis (PCA) or linear discriminant analysis (LDA). Results indicated that peony seed oil was highly enriched in α-linolenic acid. Although the iodine value can be used to detect some adulterants by measuring unsaturation, it was not able to detect all four potential adulterants. In contrast, the E-nose can rapidly identify adulterated peony seed oil by sampling vapor. Data analyses using PCA and LDA show that LDA more effectively clusters the data, discriminates between pure and adulterated oil, and can detect adulteration at the 10% level. E-nose combined with LDA suitable for detection of peony seed oil adulteration. [ABSTRACT FROM AUTHOR]

To investigate soluble sugar metabolism and its relationship to chilling injury (CI), loquat fruits were stored at 0 and 5 °C for 5 weeks. CI symptoms were monitored during storage, and soluble sugar content and related enzyme activities were measured. Enzymes activities and substrate levels in the ascorbate-glutathione (AsA-GSH) cycle were also determined. Fruit at 0 °C had lower sucrose levels and higher levels of glucose and fructose than fruit maintained at 5 °C, and also manifested less severe CI symptoms. Fruit at 0 °C also exhibited increased activities of acid invertase, neutral invertase, sucrose phosphatesynthase and sucrose synthase. AsA-GSH cycle activity at 0 °C was much higher than that at 5 °C. Glucose levels correlated positively with levels of AsA and GSH and ascorbate peroxidase (APX) activity. The increased glucose levels are sufficient to account for the chilling tolerance of loquat fruit. [ABSTRACT FROM AUTHOR]

Correction to: I Nature Communications i https://doi.org/10.1038/s41467-020-18832-8, published online 09 October 2020 The original version of this Article contained an error in Fig. These authors contributed equally: Xiaoyu Tu, María Katherine Mejía-Guerra. [Extracted from the article]

Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. [ABSTRACT FROM AUTHOR]

In epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. Current approaches to the association detection claim whether a cytosine-phosphate-guanine (CpG) site is associated with the phenotype or not at aggregate level and can suffer from low statistical power. Here, we propose a statistical method, HIgh REsolution (HIRE), which not only improves the power of association detection at aggregate level as compared to the existing methods but also enables the detection of risk-CpG sites for individual cell types. Cellular heterogeneity is one of the major confounding factors in EWAS studies. Here the authors present a statistical method, HIgh REsolution (HIRE), which enables the detection of risk-CpG sites for individual cell types. [ABSTRACT FROM AUTHOR]

Atrial Fibrillation (AF) is common in the elderly and Sestrins (Sesns) have been suggested to prevent age-related pathologies. The aim of this study was to investigate the effects of Sesns in AF. Clinical data were collected and a small sample of atrial appendage and atrium was obtained from patients undergoing valve repairment. The expression of Sesn1, Sesn2, and Sesn3 was significantly higher in patients with permanent atrial fibrillation (PmAF) than that in sinus rhythm (SR), and further greater in the left atrium than the right in PmAF patients. Superoxide anion and malondialdehyde were enhanced and positively correlated to the protein expression of Sesn1/2/3. Reactive oxygen species (ROS) production and Ca2+ overload were significantly decreased and cell survival was enhanced by overexpression of Sesns 1/2/3 in cultured HL-1 cells. Conversely, knockdown of Sesn1/2/3 resulted in significantly increased ROS and Ca2+ overload. In addition, the overexpression of Sesn1/2 significantly reduced the proliferation of fibroblasts, as well as decreased the protein expression of collagen and fibronectin1 in angiotensin II-stimulated cardiac fibroblasts. Our study demonstrated for the first time that Sesns expression is significantly up-regulated in AF, which therefore may protect hearts against oxidative damage and atrial fibrosis. [ABSTRACT FROM AUTHOR]

Eukaryotic elongation factor 1 alpha (eEF1A) is an essential component of the translational apparatus. In the present study, eEF1A1b was isolated from the Nile tilapia. Real-time PCR and Western blot revealed that eEF1A1b was expressed highly in the testis from 90 dah (days after hatching) onwards. In situ hybridization and immunohistochemistry analyses showed that eEF1A1b was highly expressed in the spermatogonia of the testis. CRISPR/Cas9 mediated mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in the F0 XY fish. Consistently, heterozygous mutation of eEF1A1b (eEF1A1b+/−) resulted in an absence of spermatocytes at 90 dah, very few spermatocytes, spermatids and spermatozoa at 180 dah, and decreased Cyp11b2 and serum 11-ketotestosterone level at both stages. Further examination of the fertilization capacity of the sperm indicated that the eEF1A1b+/− XY fish were infertile due to abnormal spermiogenesis. Transcriptomic analyses of the eEF1A1b+/− testis from 180 dah XY fish revealed that key elements involved in spermatogenesis, steroidogenesis and sperm motility were significantly down-regulated compared with the control XY. Transgenic overexpression of eEF1A1b rescued the spermatogenesis arrest phenotype of the eEF1A1b+/− testis. Taken together, our data suggested that eEF1A1b is crucial for spermatogenesis and male fertility in the Nile tilapia. [ABSTRACT FROM AUTHOR]