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Chen, Z.-X.

Publications and source records attributed to Chen, Z.-X..

7 recordsLinked to original sources

MicroRNA-383-5p alleviates hemorrhagic transformation and improves outcomes after endovascular recanalization for acute ischemic stroke

BackgroundHemorrhage transformation (HT) after reperfusion therapy is linked with poor outcomes in acute ischemic stroke patients. This study aimed to determine the role of neuronal microRNA-383 in alleviating HT-associated injury using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation reoxygenation (OGD/R) models. MethodsIn neurons following OGD/R, the family of miR-383 and NADPH oxidase (NOX) expression was evaluated. After miR-383-5p intervention and small interfering RNA, reactive oxygen species (ROS) and neuronal injury were assessed. Two hundred and five hyperglycemic rats were used to establish the HT model induced by mechanical reperfusion after 5-hour MCAO, followed by 3 and 6 hours of reperfusion, and treated with intravenous administration of miR-383-5p agomir before reperfusion. Brain water content, hemorrhage severity, infarct volume, blood-brain barrier (BBB) disruption, neuronal apoptosis, ROS production, miR-383-5p and NOX4 expression, and BBB-associated proteins were assessed. ResultsMiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. Elevating miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression as a target of miR-383-5p, shown in OGD/R-treated neurons. In the MCAO model, increased miR-383-5p suppressed NOX4 upregulation, alleviated brain edema, infarct volume, and hemorrhage severity, reduced neuronal apoptosis and ROS overproduction, and preserved BBB integrity after mechanical reperfusion for ischemia, thereby improving short-term neurological outcomes. ConclusionsMiR-383-5p alleviates oxidative stress injury and neuronal apoptosis, and preserves BBB integrity by regulating NOX4. Neuronal miR-383-5p could become a potential target for intervention to decrease HT and ameliorate outcomes in endovascular reperfusion treatment for acute ischemic stroke.

neuroscience↗

Enhanced Functional Potential of Pseudogene-associated lncRNA Genes in Mammals

The functional significance of long non-coding RNAs (lncRNAs) remains a subject of debate, largely due to the complexity and cost associated with their validation experiments. However, emerging evidence suggests that pseudogenes, once viewed as genomic relics, may contribute to the origin of functional lncRNA genes. In this study spanning eight species, we systematically identified pseudogene-associated lncRNA genes using our PacBio long-read sequencing data and published RNA-seq data. Our investigation revealed that pseudogene-associated lncRNA genes exhibit heightened functional attributes compared to their non-pseudogene-associated counterparts. Notably, these pseudogene-associated lncRNAs show protein-binding proficiency, positioning them as potent regulators of gene expression. In particular, pseudogene-associated sense lncRNAs retain protein-binding capabilities inherited from parent genes of pseudogenes, thereby demonstrating greater protein-binding proficiency. Through detailed functional characterization, we elucidated the unique advantages and conserved roles of pseudogene-associated lncRNA genes, particularly in the context of gene expression regulation and DNA repair. Leveraging cross-species expression profiling, we demonstrated the prominent contribution of pseudogene-associated lncRNA genes to aging-related transcriptome changes across nine human tissues and eight mouse tissues. Overall, our findings demonstrate enhanced functional attributes of pseudogene-associated lncRNA genes and shed light on their conserved and close association with aging.

genomics↗

A landscape of differentiated biological processes involved in the initiation of sex differentiation in zebrafish

Zebrafish (Danio rerio) has been used as a promising animal model to study gonadal development and gametogenesis. Although previous studies have identified critical molecules participating in zebrafish gonad differentiation, a landscape view of the biological processes involved in this process is still lacking. Here we isolated intact zebrafish differentiating gonads, at 25 days post-fertilization (dpf) and 30 dpf, and conducted RNA-seq analysis between the juvenile gonads that tended to develop into ovaries or testes. Our study demonstrates that the juvenile ovary and testis at 25 dpf and 30 dpf are different at the level of biological process. During ovary differentiation, the biological processes related to metabolic activities in production of energy and maternal substances, RNA degradation, and DNA repair were enriched. During testis differentiation, the biological processes related to cell proliferation, differentiation, and morphogenesis were enriched, with a total of 15 signaling pathways. Notably, we reveal that the immune-related processes are extensively involved in the regulation of testis development. Overall, this study provides a landscape of differentiated biological processes and novel insights into the initiation of sex differentiation in zebrafish.

developmental biology↗

Dynamic Spatial-Temporal Expression Ratio of X Chromosome to Autosomes but Stable Dosage Compensation in Mammals

In the evolutionary model of dosage compensation, per-allele expression level of the X chromosome was proposed to have two-fold upregulation, compensating for its dose reduction in males (XY) compared to females (XX). However, the upregulation of X chromosome is still in dispute, and comprehensive evaluations are still lacking. By integrating multi-omics datasets in mammals, we investigated the expression ratios and underlying pattern of X to autosomes (X:AA ratio) and X to orthologs (X:XX ratio) at the transcriptome, translatome, and proteome layers. The results indicated a dynamic spatial-temporal X:AA ratio during development in human and mouse. Meanwhile, by tracing the evolution of orthologous gene expressions in chicken, platypus, and opossum, we found a constant expression ratio between X-linked genes in human and their autosomal orthologs in other species (X:XX ~1) across tissues and developmental stages, demonstrating stable dosage compensation in mammals. We also revealed that different epigenetic regulations could shape the higher tissue- and stage-specificity of X-linked gene expression, and affect X:AA ratios. We conclude that the dynamics of X:AA ratios are attributed to the different gene contents and expression preferences of the X chromosome, instead of the stable dosage compensation.

evolutionary biology↗

GenOrigin: A Comprehensive Protein-coding Gene Origination Database on the Evolutionary Timescale of Life

The origination of new genes contributes to the biological diversity of life. New genes may quickly build their own network in the genomes, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific gene, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically dated the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using protein-family-based pipeline with Wagner parsimony algorithm. We also collected gene age estimate data from other studies and uniformed the gene age estimates to time ranges in million years for comparison across studies. All the data were cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a userfriendly new database of gene age estimates, where users can browse gene age estimates by species, age and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, was provided to researchers for exploring gene functions.

evolutionary biology↗

Enriched G-quadruplexes on the Drosophila Male X Chromosome Function as Insulators of Dosage Compensation Complex

The evolution of sex chromosomes has resulted in half X chromosome dosage in males as females. Dosage compensation, or the two-fold upregulation in males, was thus evolved to balance the gene expression between sexes. However, the step-wise evolutionary trajectory of dosage compensation during Y chromosome degeneration is still unclear. Here, we show that the specific structured elements G-quadruplexes (G4s) are enriched on the X chromosome in Drosophila melanogaster. Meanwhile, on the X chromosome, the G4s are underrepresented on the H4K16 acetylated regions and the binding sites of dosage compensation complex male-specific lethal (MSL) complex. Peaks of G4 density and potential are observed at the flanking regions of MSL binding sites, suggesting G4s act as insulators to precisely up-regulate certain regions in males. Thus, G4s may be involved in the evolution of dosage compensation process through fine-tuning one-dose proto-X chromosome regions around MSL binding sites during the gradual Y chromosome degeneration.\n\nOne Sentence SummaryG-quadruplexes act as insulators to precisely up-regulate X chromosome in males.

evolutionary biology↗

pyMeSHSim: an integrative python package to realize biomedical named entity recognition, normalization and comparison

SummaryComputing semantic similarity between two texts, like disease descriptions, has become important for many biomedical text mining applications. Here, we present PyMeSHSim, which is an integrative, lightweight and data-rich MeSH toolkit that recognizes biomedical named entities (bio-NEs) from texts, maps the bio-NEs to the controlled vocabulary MeSH and measures the semantic similarity between the MeSH terms.\n\nAvailabilityPackages source code and test datasets are available under the GPLv3 license at https://github.com/luozhhub/pyMeSHSim\n\nContactzhen-xia.chen@mail.hzau.edu.cn or zhy630@mail.hzau.edu.cn

bioinformatics↗