KnockTF 2.0: a comprehensive gene expression profile database with knockdown/knockout of transcription (co-)factors in multiple species.

Transcription factors (TFs), transcription co-factors (TcoFs) and their target genes perform essential functions in diseases and biological processes. KnockTF 2.0 (http://www.licpathway.net/KnockTF/index.html) aims to provide comprehensive gene expression profile datasets before/after T(co)F knockdown/knockout across multiple tissue/cell types of different species. Compared with KnockTF 1.0, KnockTF 2.0 has the following improvements: (i) Newly added T(co)F knockdown/knockout datasets in mice, Arabidopsis thaliana and Zea mays and also an expanded scale of datasets in humans. Currently, KnockTF 2.0 stores 1468 manually curated RNA-seq and microarray datasets associated with 612 TFs and 172 TcoFs disrupted by different knockdown/knockout techniques, which are 2.5 times larger than those of KnockTF 1.0. (ii) Newly added (epi)genetic annotations for T(co)F target genes in humans and mice, such as super-enhancers, common SNPs, methylation sites and chromatin interactions. (iii) Newly embedded and updated search and analysis tools, including T(co)F Enrichment (GSEA), Pathway Downstream Analysis and Search by Target Gene (BLAST). KnockTF 2.0 is a comprehensive update of KnockTF 1.0, which provides more T(co)F knockdown/knockout datasets and (epi)genetic annotations across multiple species than KnockTF 1.0. KnockTF 2.0 facilitates not only the identification of functional T(co)Fs and target genes but also the investigation of their roles in the physiological and pathological processes.

eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse.

Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs.

LncSEA 2.0: an updated platform for long non-coding RNA related sets and enrichment analysis.

Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs.

Altered Resting-State Amygdalar Functional Connectivity in Primary Angle-Closure Glaucoma Patients.

BACKGROUND: Glaucoma patients frequently present with depressive symptoms, the development of which is closely associated with amygdalar activity. However, no studies to date have documented glaucoma-related changes in the functional connectivity (FC) of the amygdala. Accordingly, resting-state functional magnetic resonance imaging (rs-fMRI) analyses were herein used to evaluate changes in amygdalar FC in primary angle-closure glaucoma (PACG) patients. METHODS: In total, this study enrolled 36 PACG patients and 33 healthy controls (HCs). Complete eye exams were conducted for all PACG patients. After the preprocessing of magnetic resonance imaging (MRI) data, the bilateral amygdala was selected as a seed point, followed by the comparison of resting-state FC between the PACG and HC groups. Then, those brain regions exhibiting significant differences between these groups were identified, and relationships between the FC coefficient values for these regions and clinical variables of interest were assessed. RESULTS: These analyses revealed that as compared to HC individuals, PACG patients exhibited reductions in FC between the amygdala and the cerebellum_8, vermis_4_5, anterior central gyrus, supplementary motor area, paracentral lobule, putamen, middle frontal gyrus, and posterior cingulate gyrus, while enhanced FC was detected between the right and left amygdala. No significant correlations between these changes in amygdalar any any disease-related clinical parameters or disease duration were noted. CONCLUSIONS: Patients with PACG exhibit extensive resting state abnormalities with respect to the FC between the amygdala and other regions of the brain, suggesting that dysregulated amygdalar FC may play a role in the pathophysiology of PACG.

The value of 3D T2-weighted SPACE sequence in the differential diagnosis of spinal arteriovenous fistula and acute transverse myelitis.

OBJECTIVE: Spinal arteriovenous fistulas (SAVF) was often neglected and misdiagnosed as acute transverse myelitis (ATM) due to its insidious onset and non-specific clinical symptoms. This study aims to investigate the differential diagnostic value of high-resolution T2-weighted volumetric sequence (3D sampling perfection with application-optimized contrasts using different flip-angle evolutions [SPACE]) in patients with SAVF and ATM. METHODS: Retrospectively analyzed the clinical and radiological findings of 32 SDAVF patients and 32 ATM patients treated at our institutions from May 2018 to January 2023. They all underwent conventional spinal MRI and T2-SPACE examination, compared their performance in identifying lesions, to estimate the value of T2 SPACE sequence in the diagnosis of SAVF and ATM patients. RESULTS: The clue of cauda equina area change (CEAC) in conventional MRI and T2-SPACE sequences is specific for the diagnosis of SAVF. The diagnostic model composed of perimedullary flow voids (PFV) and CEAC has good diagnostic performance (AUCMRI = 0.95; AUCSPACE = 0.935). Compared with conventional MRI, the T2-SPACE sequence has a higher detection rate, sensitivity, and negative predictive value for PFV and CEAC in SAVF patients, but lower specificity and positive predictive value. In T2-SPACE images, there are significant differences in the distribution range, quadrant, and maximum diameter of PFV vessels between SAVF and ATM patients. Moreover, T2-SPACE sequence can determine the site of fistula in most SAVF patients preferably, and the inter-rater agreement was good in the assessment of the fistula. CONCLUSION: The CEAC is a new and useful clue for the diagnosis of thoracolumbar SAVF. And T2-SPACE sequence can more intuitively observe the lesions of SAVF, has good differential diagnostic value for SAVF and ATM patients.

Assessment of Morphological Features and Imaging Characteristics of Patients with Intracranial Artery Dissection: A High-Resolution MRI Study.

BACKGROUND: Intracranial artery dissection (IAD) is a pathological dissection of the arterial wall. .However, the morphological features and imaging characteristics of patients with intracranial artery dissection (IAD) remain poorly understood. METHODS: The study reports on 70 IAD patients (30 culprit and 40 non-culprit). All participants underwent high-resolution magnetic resonance imaging (HR-MRI) scans. The morphological features and imaging characteristics of artery dissection were carefully investigated. Demographics and clinical characteristics of culprit and non-culprit patients were also collected. Apparent differences between the two groups, which could be used as biomarkers for ischemic event caused by the culprit dissection, were identified by receiver operating characteristic (ROC) curve analysis. RESULTS: The IAD patients studied could be classified into five different types on the basis of morphological features: classical dissection (n = 31), fusiform aneurysm (n = 2), long dissected aneurysm (n = 9), dolichoectatic dissecting aneurysm (n = 6), and saccular aneurysm (n = 22). The direct sites of artery dissection (double lumen and intimal flap) can be seen in most IAD patients on HR-MRI. Additionally, the presence of hypertension, double lumen and intimal flap were associated with culprit lesions and might be considered biomarkers for the ischemic event caused by the culprit dissection. CONCLUSIONS: Analysis showed that HR-MRI allowed easy visualization of abnormal morphology of artery dissection lesions. This was of great significance for the diagnosis of IAD and gave a better understanding of its pathophysiological mechanism.

SCInter: A comprehensive single-cell transcriptome integration database for human and mouse.

Single-cell RNA sequencing (scRNA-seq), which profiles gene expression at the cellular level, has effectively explored cell heterogeneity and reconstructed developmental trajectories. With the increasing research on diseases and biological processes, scRNA-seq datasets are accumulating rapidly, highlighting the urgent need for collecting and processing these data to support comprehensive and effective annotation and analysis. Here, we have developed a comprehensive Single-Cell transcriptome integration database for human and mouse (SCInter, https://bio.liclab.net/SCInter/index.php), which aims to provide a manually curated database that supports the provision of gene expression profiles across various cell types at the sample level. The current version of SCInter includes 115 integrated datasets and 1016 samples, covering nearly 150 tissues/cell lines. It contains 8016,646 cell markers in 457 identified cell types. SCInter enabled comprehensive analysis of cataloged single-cell data encompassing quality control (QC), clustering, cell markers, multi-method cell type automatic annotation, predicting cell differentiation trajectories and so on. At the same time, SCInter provided a user-friendly interface to query, browse, analyze and visualize each integrated dataset and single cell sample, along with comprehensive QC reports and processing results. It will facilitate the identification of cell type in different cell subpopulations and explore developmental trajectories, enhancing the study of cell heterogeneity in the fields of immunology and oncology.

Cis-Cardio: A comprehensive analysis platform for cardiovascular-relavant cis-regulation in human and mouse.

Cis-regulatory elements are important molecular switches in controlling gene expression and are regarded as determinant hubs in the transcriptional regulatory network. Collection and processing of large-scale cis-regulatory data are urgent to decipher the potential mechanisms of cardiovascular diseases from a cis-regulatory element aspect. Here, we developed a novel web server, Cis-Cardio, which aims to document a large number of available cardiovascular-related cis-regulatory data and to provide analysis for unveiling the comprehensive mechanisms at a cis-regulation level. The current version of Cis-Cardio catalogs a total of 45,382,361 genomic regions from 1,013 human and mouse epigenetic datasets, including ATAC-seq, DNase-seq, Histone ChIP-seq, TF/TcoF ChIP-seq, RNA polymerase ChIP-seq, and Cohesin ChIP-seq. Importantly, Cis-Cardio provides six analysis tools, including region overlap analysis, element upstream/downstream analysis, transcription regulator enrichment analysis, variant interpretation, and protein-protein interaction-based co-regulatory analysis. Additionally, Cis-Cardio provides detailed and abundant (epi-) genetic annotations in cis-regulatory regions, such as super-enhancers, enhancers, transcription factor binding sites (TFBSs), methylation sites, common SNPs, risk SNPs, expression quantitative trait loci (eQTLs), motifs, DNase I hypersensitive sites (DHSs), and 3D chromatin interactions. In summary, Cis-Cardio is a valuable resource for elucidating and analyzing regulatory cues of cardiovascular-specific cis-regulatory elements. The platform is freely available at http://www.licpathway.net/Cis-Cardio/index.html.

Landscape and significance of human super enhancer-driven core transcription regulatory circuitry.

A core transcription regulatory circuitry (CRC) is an interconnected self-regulatory circuitry that is formed by a group of core transcription factors (TFs). These core TFs collectively regulate gene expression by binding not only to their own super enhancers (SEs) but also to the SEs of one another. For most human tissue/cell types, a global view of CRCs and core TFs has not been generated. Here, we identified numerous CRCs using two identification methods and detailed the landscape of the CRCs driven by SEs in large cell/tissue samples. The comprehensive biological analyses, including sequence conservation, CRC activity and genome binding affinity were conducted for common TFs, moderate TFs, and specific TFs, which exhibit different biological features. The local module located from the common CRC network highlighted the essential functions and prognostic performance. The tissue-specific CRC network was highly related to cell identity. Core TFs in tissue-specific CRC networks exhibited disease markers, and had regulatory potential for cancer immunotherapy. Moreover, a user-friendly resource named CRCdb (http://www.licpathway.net/crcdb/index.html) was developed, which contained the detailed information of CRCs and core TFs used in this study, as well as other interesting results, such as the most representative CRC, frequency of TFs, and indegree/outdegree of TFs.

Engineering Yarrowia lipolytica to produce nutritional fatty acids: Current status and future perspectives.

Due to their vital physiological functions, nutritional fatty acids have great potential as nutraceutical food supplements for preventing an array of diseases such as inflammation, depression, arthritis, osteoporosis, diabetes and cancer. Microbial biosynthesis of fatty acids follows the trend of sustainable development, as it enables green, environmentally friendly and efficient production. As a natural oleaginous yeast, Yarrowia lipolytica is especially well-suited for the production of fatty acids. Moreover, it has a variety of genetic engineering tools and novel metabolic engineering strategies that make it a robust workhorse for the production of an array of value-added products. In this review, we summarize recent advances in metabolic engineering strategies for accumulating nutritional fatty acids in Y. lipolytica, including conjugated fatty acids and polyunsaturated fatty acids. In addition, the future prospects of nutritional fatty acid production using the Y. lipolytica platform are discussed in light of the current progress, challenges, and trends in this field. Finally, guidelines for future studies are also emphasized.

Altered functional connectivity of the thalamus in primary angle-closure glaucoma patients: A resting-state fMRI study.

Background and objectives: Glaucoma is one of the leading irreversible causes of blindness worldwide, and previous studies have shown that there is abnormal functional connectivity (FC) in the visual cortex of glaucoma patients. The thalamus is a relay nucleus for visual signals; however, it is not yet clear how the FC of the thalamus is altered in glaucoma. This study investigated the alterations in thalamic FC in patients with primary angle-closure glaucoma (PACG) by using resting-state functional MRI (rs-fMRI). We hypothesized that PACG patients have abnormal FC between the thalamus and visual as well as extravisual brain regions. Methods: Clinically confirmed PACG patients and age- and gender-matched healthy controls (HCs) were evaluated by T1 anatomical and functional MRI on a 3 T scanner. Thirty-four PACG patients and 33 HCs were included in the rs-fMRI analysis. All PACG patients underwent complete ophthalmological examinations; included retinal nerve fiber layer thickness (RNFLT), intraocular pressure (IOP), average cup-to-disc ratio (A-C/D), and vertical cup-to-disc ratio (V-C/D). After the MRI data were preprocessed, the bilateral thalamus was chosen as the seed point; and the differences in resting-state FC between groups were evaluated. The brain regions that significantly differed between PACG patients and HCs were identified, and the correlations were then evaluated between the FC coefficients of these regions and clinical variables. Results: Compared with the HCs, the PACG patients showed decreased FC between the bilateral thalamus and right transverse temporal gyrus, between the bilateral thalamus and left anterior cingulate cortex, and between the left thalamus and left insula. Concurrently, increased FC was found between the bilateral thalamus and left superior frontal gyrus in PACG patients. The FC between the bilateral thalamus and left superior frontal gyrus was positively correlated with RNFLT and negatively correlated with the A-C/D and V-C/D. The FC between the left thalamus and left insula was negatively correlated with IOP. Conclusion: Extensive abnormal resting-state functional connections between the thalamus and visual and extravisual brain areas were found in PACG patients, and there were certain correlations with clinical variables, suggesting that abnormal thalamic FC plays an important role in the progression of PACG.