NRSF regulates age-dependently cognitive ability and its conditional knockout in APP/PS1 mice moderately alters AD-like pathology.

NRSF/REST (neuron-restrictive silencer element, also known as repressor element 1-silencing transcription factor), plays a key role in neuronal homeostasis as a transcriptional repressor of neuronal genes. NRSF/REST relates to cognitive preservation and longevity of humans, but its specific functions in age-dependent and Alzheimer's disease (AD)-related memory deficits remain unclear. Here, we show that conditional NRSF/REST knockout either in the dorsal telencephalon or specially in neurons induced an age-dependently diminished retrieval performance in spatial or fear conditioning memory tasks and altered hippocampal synaptic transmission and activity-dependent synaptic plasticity. The NRSF/REST deficient mice were also characterized by an increase of activated glial cells, complement C3 protein and the transcription factor C/EBPß in the cortex and hippocampus. Reduction of NRSF/REST by conditional depletion upregulated the activation of astrocytes in APP/PS1 mice, and increased the C3-positive glial cells, but did not alter the Aß loads and memory retrieval performances of 6- and 12-month-old APP/PS1 mice. Simultaneously, overexpression of NRSF/REST improved cognitive abilities of aged wild type, but not in AD mice. These findings demonstrated that NRSF/REST is essential for the preservation of memory performance and activity-dependent synaptic plasticity during aging and takes potential roles in the onset of age-related memory impairments. However, while altering the glial activation, NRSF/REST deficiency does not interfere with the Aß deposits and the electrophysiological and cognitive AD-like pathologies.

Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson's disease.

Neuroinflammation is one of the core pathological features of Parkinson's disease (PD). Innate immune cells play a crucial role in the progression of PD. Microglia, the major innate immune cells in the brain, exhibit innate immune memory effects and are recognized as key regulators of neuroinflammatory responses. Persistent modifications of microglia provoked by the first stimuli are pivotal for innate immune memory, resulting in an enhanced or suppressed immune response to second stimuli, which is known as innate immune training and innate immune tolerance, respectively. In this study, LPS was used to establish in vitro and in vivo models of innate immune memory. Microglia-specific Hif-1α knockout mice were further employed to elucidate the regulatory role of HIF-1α in innate immune memory and MPTP-induced PD pathology. Our results showed that different paradigms of LPS could induce innate immune training or tolerance in the nigrostriatal pathway of mice. We found that innate immune tolerance lasting for one month protected the dopaminergic system in PD mice, whereas the effect of innate immune training was limited. Deficiency of HIF-1α in microglia impeded the formation of innate immune memory and exerted protective effects in MPTP-intoxicated mice by suppressing neuroinflammation. Therefore, HIF-1α is essential for microglial innate immune memory and can promote neuroinflammation associated with PD.

Actinoplanes sandaracinus sp. nov., a novel ligninase- producing and cellulose-degrading actinobacterium isolated from soil.

A novel ligninase-producing and cellulose-degrading actinobacterium, designated strain NEAU-A12T, was isolated from a soil sample collected from Aohan banner, Chifeng City, Inner Mongolia Autonomous Region, PR China. A polyphasic taxonomic study was used to establish the status of strain NEAU-A12T. 16S rRNA gene sequence analysis revealed that strain NEAU-A12T belonged to the genus Actinoplanes and showed the highest similarity (98.3 %) to Actinoplanes palleronii DSM 43940T, while showing less than 98.3 % similarity to other members of the genus Actinoplanes. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and glycosylphosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be arabinose, glucose and xylose. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The major fatty acids were C15 : 0, C16 : 0, C16 : 1 ω7c and C17 : 0. Meanwhile, genomic analysis revealed a genome size of 10 192 524 bp and a DNA G+C content of 70.6 mol%, and indicated that strain NEAU-A12T had the potential to degrade lignin and cellulose, as well as produce bioactive compounds. In addition, the average nucleotide identity values between strain NEAU-A12T and its reference strains A. palleronii DSM 43940T, Actinoplanes regularis DSM 43151T, Actinoplanes philippinensis DSM 43019T, Actinoplanes xinjiangensis DSM 45184T and Actinoplanes italicus DSM 43146T were 80.3, 80.3, 84.1, 84.3 and 84.0 %, respectively. The levels of digital DNA-DNA hybridization between them were found to be 23.6 % (21.3-26.1 %), 23.8 % (21.5-26.3 %), 28.3 % (25.9-30.8 %), 28.6 % (26.0-30.9 %) and 28.4 % (26.2-31.1 %), respectively. Based on phenotypic, chemotaxonomic and genotypic data, strain NEAU-A12T is considered to represent a novel species of the genus Actinoplanes, for which the name Actinoplanes sandaracinus sp. nov. is proposed, with NEAU-A12T (=CCTCC AA 2020039T=DSM 112043T) as the type strain.

NOD-like receptor NLRC5 promotes neuroinflammation and inhibits neuronal survival in Parkinson's disease models.

Parkinson's disease (PD) is mainly characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and neuroinflammation mediated by overactivated microglia and astrocytes. NLRC5 (nucleotide-binding oligomerization domain-like receptor family caspase recruitment domain containing 5) has been reported to participate in various immune disorders, but its role in neurodegenerative diseases remains unclear. In the current study, we found that the expression of NLRC5 was increased in the nigrostriatal axis of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD, as well as in primary astrocytes, microglia and neurons exposed to different neurotoxic stimuli. In an acute MPTP-induced PD model, NLRC5 deficiency significantly reduced dopaminergic system degeneration and ameliorated motor deficits and striatal inflammation. Furthermore, we found that NLRC5 deficiency decreased the expression of the proinflammatory genes IL-1ß, IL-6, TNF-α and COX2 in primary microglia and primary astrocytes treated with neuroinflammatory stimuli and reduced the inflammatory response in mixed glial cells in response to LPS treatment. Moreover, NLRC5 deficiency suppressed activation of the NF-κB and MAPK signaling pathways and enhanced the activation of AKT-GSK-3ß and AMPK signaling in mixed glial cells. Furthermore, NLRC5 deficiency increased the survival of primary neurons treated with MPP+ or conditioned medium from LPS-stimulated mixed glial cells and promoted activation of the NF-κB and AKT signaling pathways. Moreover, the mRNA expression of NLRC5 was decreased in the blood of PD patients compared to healthy subjects. Therefore, we suggest that NLRC5 promotes neuroinflammation and dopaminergic degeneration in PD and may serve as a marker of glial activation.

Nocardia rosealba sp. nov., a novel ligninase-producing Actinobacterium isolated from soil.

A novel ligninase-producing actinomycete, designated strain NEAU-G4T, was isolated from a soil sample and subjected to a polyphasic taxonomic study to establish its status. According to 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Nocardia, with the highest sequence similarity to Nocardia ignorata DSM 44496T (99.2 %). The whole-cell sugars contained galactose and arabinose. The amino acid of the cell wall was determined to be meso-diaminopimelic acid. The major fatty acids (>10 %) were C16 : 0, C18 : 1 ω9c, C18 : 0 and C16 : 1 ω7c. The predominant menaquinone was identified as MK-8(H6, ω-cycl). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Strain NEAU-G4T had a draft genome size of 6 405 167 bp, annotated with 5815 protein-coding genes. The DNA G+C content was 67.6 mol%. Phylogenetic analysis using the 16S rRNA gene and whole-genome sequences showed that strain NEAU-G4T formed a stable phyletic line with N. ignorata DSM 44496T. The digital DNA-DNA hybridization and average nucleotide identity values between them were 63.7 % (60.8-66.5 %) and 95.5 %, respectively. Moreover, genomic analysis indicated that strain NEAU-G4T had the potential to degrade lignin and produce bioactive compounds. On the basis of genotypic analysis, physiological data, as well as phenotypic and chemotaxonomic characterizations, it is concluded that the organism be classified as representing a novel species of the genus Nocardia, for which the name Nocardia rosealba sp. nov. is proposed. The type strain is NEAU-G4T (=CCTCC AA 2020038T=DSM 111936T).

Saccharothrix luteola sp. nov., a novel cellulose-degrading actinobacterium isolated from soil and emended description of the genus Saccharothrix.

A novel cellulose-degrading actinobacterium, designated strain NEAU-S10T, was isolated from soil collected from Chifeng, Inner Mongolia Autonomous Region, PR China, and characterized using a polyphasic approach. Pairwise similarity of the 16S rRNA gene sequence showed that strain NEAU-S10T was a representative of Saccharothrix and was closely related to Saccharothrix carnea NEAU-yn17T (99.2 %), Saccharothrix saharensis SA152T (99.0 %), Saccharothrix texasensis DSM 44231T (98.5 %) and Saccharothrix xinjiangensis NBRC 101911T (98.5 %). Physiological and chemotaxonomic characteristics of the strain further supported its affiliation to the genus Saccharothrix. The whole-cell sugars contained galactose, ribose and mannose. The polar lipids contained diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The predominant menaquinones were MK-9(H0), MK-9(H2), MK-9(H4) and MK-10(H4). The major fatty acids were iso-C16 : 0, C16 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C17 : 0. The genomic DNA G+C content was 71.8 mol%. The levels of digital DNA-DNA hybridization between isolate and S. carnea NEAU-yn17T, S. saharensis SA152T and S. texasensis DSM 44231T were 40.1 % (37.6-42.6 %), 38.soap8 % (36.3-41.3 %) and 44.8 % (42.2-47.3 %) and the ANI values between them were determined to be 90.2, 89.8 and 91.7 %, the results indicated that strain NEAU-S10T could be distinguished from its reference strains. The assembled genome sequence of strain NEAU-S10T was found to be 10 305 394 bp long. The NCBI Prokaryotic Genome Annotation Pipeline (PGAP) revealed 8 994 protein-coding genes. Genomic analysis and Congo red staining test indicated that strain NEAU-S10T had the potential to degrade cellulose. The genomic and phenotypic results indicate that strain NEAU-S10T represents a novel species of the genus Saccharothrix, for which the name Saccharothrix luteola sp. nov. is proposed, with NEAU-S10T (=CCTCC AA 2020037T=JCM 34800T) as the type strain.

Complex impact of DNA methylation on transcriptional dysregulation across 22 human cancer types.

Accumulating evidence has demonstrated that transcriptional regulation is affected by DNA methylation. Understanding the perturbation of DNA methylation-mediated regulation between transcriptional factors (TFs) and targets is crucial for human diseases. However, the global landscape of DNA methylation-mediated transcriptional dysregulation (DMTD) across cancers has not been portrayed. Here, we systematically identified DMTD by integrative analysis of transcriptome, methylome and regulatome across 22 human cancer types. Our results revealed that transcriptional regulation was affected by DNA methylation, involving hundreds of methylation-sensitive TFs (MethTFs). In addition, pan-cancer MethTFs, the regulatory activity of which is generally affected by DNA methylation across cancers, exhibit dominant functional characteristics and regulate several cancer hallmarks. Moreover, pan-cancer MethTFs were found to be affected by DNA methylation in a complex pattern. Finally, we investigated the cooperation among MethTFs and identified a network module that consisted of 43 MethTFs with prognostic potential. In summary, we systematically dissected the transcriptional dysregulation mediated by DNA methylation across cancer types, and our results provide a valuable resource for both epigenetic and transcriptional regulation communities.

Computed tomography-guided coil localization for scapular-blocked lung nodules.

PURPOSE: To investigate the clinical efficacy, feasibility, and safety of the preoperative computed tomography (CT)-guided coil localization (CL) approach for scapula-blocked lung nodules (SBLNs). MATERIAL AND METHODS: A total of 123 patients with LNs were treated via CT-guided CL and subsequent VATS-guided wedge resection from January 2015 to June 2020. Of these patients, 12 (9.8%) exhibited SBLNs and underwent CT-guided CL. Technical success of localization and video-assisted thoracoscopic surgery (VATS)-guided wedge resection, and localization-related complications were recorded and analyzed. RESULTS: The technical success rate of CT-guided CL was 100%. Each patient was placed with one coil. The mean duration of CT-guided CL was 14.7 ± 2.7 min. One patient (8.3%) developed asymptomatic pneumothorax, which has not impacted the subsequent VATS procedure. Successful VATS-guided wedge resection of these SBLNs was achieved in all patients, with no instances of conversion to thoracotomy. Additional lobectomy was performed in three patients. The mean duration of the VATS procedure and blood loss were 143.8 ± 95.5 min and 110.0 ± 82.0 ml, respectively. CONCLUSIONS: The approach of CT-guided CL could be safely and easily utilized to facilitate high rates of success when conducting the VATS-guided wedge resection of SBLNs.

Systematic review of computational methods for identifying miRNA-mediated RNA-RNA crosstalk.

Posttranscriptional crosstalk and communication between RNAs yield large regulatory competing endogenous RNA (ceRNA) networks via shared microRNAs (miRNAs), as well as miRNA synergistic networks. The ceRNA crosstalk represents a novel layer of gene regulation that controls both physiological and pathological processes such as development and complex diseases. The rapidly expanding catalogue of ceRNA regulation has provided evidence for exploitation as a general model to predict the ceRNAs in silico. In this article, we first reviewed the current progress of RNA-RNA crosstalk in human complex diseases. Then, the widely used computational methods for modeling ceRNA-ceRNA interaction networks are further summarized into five types: two types of global ceRNA regulation prediction methods and three types of context-specific prediction methods, which are based on miRNA-messenger RNA regulation alone, or by integrating heterogeneous data, respectively. To provide guidance in the computational prediction of ceRNA-ceRNA interactions, we finally performed a comparative study of different combinations of miRNA-target methods as well as five types of ceRNA identification methods by using literature-curated ceRNA regulation and gene perturbation. The results revealed that integration of different miRNA-target prediction methods and context-specific miRNA/gene expression profiles increased the performance for identifying ceRNA regulation. Moreover, different computational methods were complementary in identifying ceRNA regulation and captured different functional parts of similar pathways. We believe that the application of these computational techniques provides valuable functional insights into ceRNA regulation and is a crucial step for informing subsequent functional validation studies.

Mapping QTL for seedling morphological and physiological traits under normal and salt treatments in a RIL wheat population.

KEY MESSAGE: The genetic basis of 27 seedling traits under normal and salt treatments was fully analyzed in a RIL wheat population, and seven QTL intervals were validated in two other genetic populations. Soil salinity seriously constrains wheat (Triticum aestivum L.) production globally by influencing its growth and development. To explore the genetic basis of salt tolerance in wheat, a recombinant inbred line (RIL) population derived from a cross between high-yield wheat cultivar Zhongmai 175 (ZM175) and salt-tolerant cultivar Xiaoyan 60 (XY60) was used to map QTL for seedling traits under normal and salt treatments based on a high-density genetic linkage map. A total of 158 stable additive QTL for 27 morphological and physiological traits were identified and distributed on all wheat chromosomes except 3A and 4D. They explained 2.35-46.43% of the phenotypic variation with a LOD score range of 2.61-40.38. The alleles from XY60 increased corresponding traits for 100 QTL, while the alleles from ZM175 had positive effects for the other 58 QTL. Nearly half of the QTL (78/158) were mapped in nine QTL clusters on chromosomes 2A, 2B, 2D, 4B, 5A, 5B, 5D, and 7D (2), respectively. To prove the reliability and potentiality in molecular marker-assisted selection (MAS), seven QTL intervals were validated in two other genetic populations. Besides additive QTL, 94 pairs of loci were detected with significant epistatic effect and 20 QTL were found to interact with treatment. This study provides a full elucidation of the genetic basis of seedling traits (especially root system-related traits) associated with salt tolerance in wheat, and the developed kompetitive allele-specific PCR markers closely linked to stable QTL would supply strong supports to MAS in salt-tolerant wheat breeding.

Rotating night shift work is associated with an increased risk of gastroesophageal reflux disease (GERD) symptoms among workers in China: A cross-sectional study.

AIMS OF THE STUDY: Increasing studies suggest a significant association between night shift work and an increased risk of type 2 diabetes, obesity and other metabolic disorders. However, the available evidence of the association of rotating night shift work with gastroesophageal reflux disease (GERD) is limited. Herein, we hypothesised a link between the GERD risk and rotating night shift work among workers in China. METHODS USED TO CONDUCT THE STUDY: A total of 2027 workers who completed a comprehensive health checkup were included. Logistic regression was used to investigate the link between rotating night shift work and the risk of GERD symptoms. Receiver operating characteristic (ROC) curve analysis was used to assess the multivariable model's diagnostic value for identifying GERD symptoms among workers. RESULTS OF THE STUDY: In total, 556 (27.4%) individuals had GERD symptoms among 2027 workers. Multivariate analysis showed five independent factors for GERD: rotating night shift work (OR = 3.66, 95% CI: 2.52-5.40), age (OR = 2.53, 95% CI: 1.67-3.78), smoking (OR = 3.70, 95% CI: 2.63-5.21), Helicobacter pylori (H. pylori) infection (OR = 0.68, 95% CI: 0.48-0.96) and obesity (OR = 3.04, 95% CI: 2.43-3.83). A five-variable model based on five independent factors provided an area under a ROC curve (AUROC) of 0.80 (95% CI: 0.78-0.81) for identifying GERD symptoms among workers. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: Rotating night shift work is independently associated with an increased risk of GERD symptoms. Moreover a five-variable model (rotating night shift work, age, smoking, H pyori infection and obesity) can help identify individuals at high risk for GERD symptoms among workers in China.

Are effect sizes in self-efficacy field changing over time? A meta-meta analysis.

Theories relating to self-efficacy have developed rapidly since Bandura first proposed the concept in 1977. In the past two decades, psychologists have carried out numerous studies to research the cultural and psychological changes in social development. The research topic of this study is whether self-efficacy changes over time. This study uses a meta-meta analysis and includes 13 meta-analyses, including 536 effect sizes, with a total sample size of 421,880. We find that individual self-efficacy increases over time, which may be related to social development trends. However, the effects of interventions on self-efficacy remain similar (Qmodel  = 1.807, df = 1, p > .05), and a possible explanation is that time effects of self-efficacy confuse the effects of intervention, because both in the intervention group and control group, the average of self-efficacy increases over time. And we find that a general decline in the predictive effects of self-efficacy (Qmodel  = 5.117, df = 1, p = .024), especially the ability to predict relatively objective variables (e.g. job performance, teaching effectiveness, and transfer of training). A possible explanation is that as social development people tend to overestimate their self-efficacy. Another possible explanation is that the effect sizes in the original studies being overrated, may due to intentional selective reporting or unintentional statistical errors.

Combinatorial epigenetic regulation of non-coding RNAs has profound effects on oncogenic pathways in breast cancer subtypes.

Although systematic genomic studies have identified a broad spectrum of non-coding RNAs (ncRNAs) that are involved in breast cancer, our understanding of the epigenetic dysregulation of those ncRNAs remains limited. Here, we systematically analysed the epigenetic alterations of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in two breast cancer subtypes (luminal and basal). Widespread epigenetic alterations of miRNAs and lncRNAs were observed in both cancer subtypes. In contrast to protein-coding genes, the majority of epigenetically dysregulated ncRNAs were shared between subtypes, but a subset of transcriptomic and corresponding epigenetic changes occurred in a subtype-specific manner. In addition, our findings suggested that various types of epi-modifications might synergistically modulate ncRNA transcription. Our observations further highlighted the complementary dysregulation of epi-modifications, particularly of miRNA members within the same family, which produced the same directed alterations as a result of diverse epi-modifications. Functional enrichment analysis revealed that epigenetically dysregulated ncRNAs were significantly involved in several hallmarks of cancers. Finally, our analysis of epigenetic modification-mediated miRNA regulatory networks revealed that cancer progression was associated with specific miRNA-gene modules in two subtypes. This study enhances understanding of the aberrant epigenetic patterns of ncRNA expression and provides new insights into the functions of ncRNAs in breast cancer subtypes.

LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network perturbations.

Gene regulatory network perturbations contribute to the development and progression of cancer, however, molecular determinants that mediate transcriptional perturbations remain a fundamental challenge for cancer biology. We show that transcriptional perturbations are widely mediated by long noncoding RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with paired lncRNA and gene expression profiles. Systematic construction of an LncRNA Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA regulatory molecules, which are expressed in multiple tissues, exhibit higher conservation. Strikingly, cancers with similar tissue origin share lncRNA modulators which perturb the regulation of cell cycle and immune response-related functions. Furthermore, we identified a large number of pan-cancer lncRNA modulators with potential clinical significance, which are differentially expressed in cancer or are strongly correlated with drug sensitivity across cell lines. Further stratification of cancer patients based on lncRNA-mediated transcriptional perturbations identifies subtypes with distinct survival rates. Finally, we made a user-friendly web interface available for exploring lncRNA-mediated transcriptional perturbations across cancer types. Our study provides a systems-level dissection of lncRNA-mediated regulatory perturbations in cancer, and also presents a valuable tool and resource for investigating the function of lncRNAs in cancer.

Covered versus uncovered stent insertion for malignant superior vena cava obstruction.

Purpose: To determine whether covered or uncovered stent insertion achieved better clinical efficacy when used to treat malignant superior vena cava (SVC) obstruction (SVCO).Material and methods: A total of 64 patients with malignant SVCO underwent stent insertion between January 2011 and March 2018 at our center. Of these, 34 were treated via uncovered stent insertion while 30 were treated via covered stent insertion. We compared the clinical effectiveness, patency of the stent, and overall survival between these two groups.Results: Both treatments achieved a 100% technical and clinical success rate, without any incidence of complications relating to the procedure. Stent dysfunction was found in one and six patients in the covered and uncovered groups during the follow-up period (1/30 vs. 6/34, p = .153), respectively. The covered stent patency period was significantly longer in the group treated with covered stents (374 vs. 317 days, p = .049), while median survival following stent insertion was 175 and 159 days, respectively, for the covered and uncovered groups (p = .784).Conclusion: Uncovered and covered stent insertion are both safe means of effectively treating patients with malignant SVCO, but covered stents achieve better patency for long-term periods than uncovered stents.

The pretreatment of chronic restraint stress exerts little impact on the progression of heart failure in mice.

Stress is a potent risk factor for depression. Chronic stress can exacerbate and induce symptoms of depression. Clinical studies suggested that depressive patients are more likely to develop coronary artery diseases. However, the causal relationship between depression and heart failure progression remains unclear. In this study, we aimed to explore the relevance between stress and heart failure (HF) in a mouse model subjected to chronic restraint stress and left anterior descending coronary artery (LAD) ligation. Mice were restrained for 3 h daily for 21 days and the processes were repeated once 3 months later. After the repeated chronic restraint stress, mice showed dramatically increased immobility time in the forced swim test, indicating a state of despair. Restrained and control mice were further subjected to LAD ligation surgery. Echocardiography was conducted 1 week, 2 weeks, and 1 month afterward. LAD-operated mice showed a significant decrease in the values of left ventricular ejection fraction (LVEF), and there was no difference in the LVEF values between the restrained and control mice. Relevant gene expression, neurotransmitter system, glial activation, and morphology of the heart-brain axis were comprehensively evaluated. We found no overall differences between the restrained and control mice with HF. Our results revealed that the repeated chronic restraint stress may have little effects on the progression of heart failure.

Methods for Identification of Protein-RNA Interaction.

The importance of RNA-protein interactions in regulation of mRNA and non-coding RNA function is increasingly appreciated. With the development of next generation high-throughput sequencing technologies, a variety of methods have been proposed to comprehensively identify RNA-protein interactions. In this chapter, we discussed the traditional and state-of-the-art technologies that were used to study RNA-protein interaction, including experimental and computational methods. To help highlight the biological significance of RNA-protein interaction in complex diseases, online resources on RNA-protein interactions were briefly discussed. Finally, we discussed the interaction among noncoding RNAs (such as long noncoding RNAs and microRNAs) and proteins, as well as the dysregulation of RNA-protein interaction in complex diseases. These summarization will ultimately provide a more complete picture for understanding of the function of RNA-protein interactions, including how these interaction assembled and how they modulate cellular function in complex diseases.

The mRNA related ceRNA-ceRNA landscape and significance across 20 major cancer types.

Cross-talk between competitive endogenous RNAs (ceRNAs) through shared miRNAs represents a novel layer of gene regulation that plays important roles in the physiology and development of cancers. However, a global view of their system-level properties across various types of cancers is still unknown. Here, we constructed the mRNA related ceRNA-ceRNA interaction landscape across 20 cancer types by systematically analyzing molecular profiles of 5203 tumors and miRNA regulations. Our study highlights the conserved features shared by pan-cancer and higher similarity within similar origin cell type. Moreover, a core ceRNA network was identified. Function analysis identified a common theme of cancer hallmarks, however they exhibit phenotype-specific connectivity patterns. Besides, we found a marked rewiring in the ceRNA program between various cancers, and further revealed conserved and rewired network ceRNA hubs in each cancer, which were tensely competitive interactions to constitute conserved and cancer-specific modules. By providing mechanistic linkage between known cancer miRNAs, their mediated ceRNA-ceRNA interactions, and the associations with known cancer hallmarks, the inferred cancer ceRNA-ceRNA interaction landscape will serve as a powerful public resource for further biological discoveries of tumorigenesis.

Fascin 1 promoted the growth and migration of non-small cell lung cancer cells by activating YAP/TEAD signaling.

Fascin 1 (Fascin actin-bundling protein 1) is an actin-binding protein. Although several studies have reported the dysregulation of Fascin 1 in non-small cell lung cancer (NSCLC), its functions in the progression of NSCLC and the related molecular mechanism were not fully understood. In this study, the expression of Fascin 1 in NSCLC tissues was determined using quantitative PCR (qPCR), and the roles of Fascin 1 in the progression of NSCLC were investigated. It was found that both the messenger RNA (mRNA) level and the protein level of Fascin 1 were upregulated in NSCLC tissues. Forced expression of Fascin 1 promoted the growth and migration of NSCLC cells, while knocking down the expression of Fascin 1 inhibited the growth, migration, and tumorigenesis of NSCLC cells. Mechanism studies showed that Fascin 1 increased the transcriptional activity of the YAP/TEAD (Yes-associated protein/TEA domain transcriptional factor) complex, and knocking down the expression of Fascin 1 attenuated the expression of target genes downstream the YAP/TEAD complex. In addition, MST1 interacted with Fascin 1. Taken together, Fascin 1 plays an oncogenic role in NSCLC by activating the transcriptional activity of the YAP/TEAD complex.

A New Method for Constructing Macrophage-Associated Predictors of Treatment Efficacy Based on Single-Cell Sequencing Analysis.

Tumor-associated macrophages (TAMs) are highly infiltrated in the tumor microenvironment (TME) of colorectal cancer (CRC) and play a vital role in CRC's development as well as prognosis. The required data were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas. Univariate Cox regression and least absolute shrinkage operator analyses were executed for model construction. TME assessment and immune prediction were performed using the ESTIMATE software package and the single sample genome enrichment analysis algorithm. The results show patients with low a TAMs risk score (TRS) had a better prognosis in both The Cancer Genome Atlas and Gene Expression Omnibus cohorts. Patients with low TRS were more sensitive to 3 chemotherapeutic agents: oxaliplatin, paclitaxel, and cisplatin ( P <0.05). TME assessment showed that the low TRS group had less infiltration of M2 macrophages and regulatory T cells, but CD4 + T cells, NK cells, and dendritic cells occupy a greater proportion of TME. Low TRS group patients have a low StromalScore and ImmuneScore but have high TumorPurity. The immune checkpoint TIM-3 gene HAVCR2 expression was significantly higher in the high TRS group. Finally, we created a nomogram including TRS for forecasting survival, and TRS was significantly associated with the clinical stage of the patients. In conclusion, the TRS serves as a reliable prognostic indicator of CRC; it predicts patient outcomes to immunotherapy and chemotherapy and provides genomic evidence for the subsequent development of modulated TAMs for treating CRC.