Biology subjects

Li, W.-X.

Publications and source records attributed to Li, W.-X..

7 recordsLinked to original sources

bioRxiv2025

Mitochondrial Genome-Based Phylogeny of Turbellarians and Evidence for Accelerated Mitochondrial Evolution in Symbiotic Species

BackgroundFlatworms are a highly diverse phylum with over 26,500 predominantly parasitic species. A minor portion of this diversity comprise predominantly free-living "turbellarians" Phylogenetic relationships within turbellarian orders remain debated, with recent mitochondrial genome studies also questioning the monophyly of the "Neoophora clade". Some unique mitochondrial gene features have also been observed in this group. Within Turbellaria, the order Rhabdocoela includes significant symbiotic lineages, such as the endosymbiotic Umagillidae, Pterastericolidae, and Graffillidae, and the ectosymbiotic Temnocephalidae, which notably exhibits characteristics akin to a parasitic lifestyle. Given evidence linking parasitic lifestyles to accelerated mitogenomic evolution, we hypothesize that similar patterns: symbiotic turbellarians have mitochondrial genomes that accelerate evolution compared to free-living turbellarians. This study presents the first complete mitochondrial genome of the ectosymbiont Craspedella pedum, provides mitogenomic insights into turbellarian phylogeny, and addressing our hypothesis. ResultsThe mitochondrial genome of Craspedella pedum is a circular DNA molecule of 18,456 base pairs, containing the standard 36 flatworm mitochondrial genes, a duplicated trnT, two cox1 pseudogene fragments, a putative atp8 gene, and several distinctive NCRs. Phylogenetic analyses based on 47 mitochondrial genomes, including the newly sequenced C. pedum and two assembled species from SRA database, using CAT-GTR model and BI and ML algorithms further confirmed that the paraphyly of the Neoophora clade and the basal position of Catenulida and Macrostomida. Different from previous study, Rhabdocoela forms a distinct clade within the turbellarians diverged immediately after Macrostomida before Polycladida and Tricladida. Within Rhabdocoela, C. pedum formed a direct sister clade with Typhloplanidae, suggesting a close phylogenetic relationship between the two. We also identified the paraphyletic of the Planoceridae of Polycladida and the unstable position of Planariidae within Tricladidain. Furthermore, we found a trend that the nad4L-nad4 gene box in turbellarians may have evolved from an overlapping state, to the insertion of a non-coding region (NCR), and subsequently to a separated configuration, correlating with species divergence. The selection pressure analysis showcased selective relaxation from free-living species of Rhabdocoela to symbiotic species of Rhabdocoela. Furthermore, we also detected a relaxation from certain tubellarian lineages to Rhabdocoela. Along with higher GORR and longer Brl, Rhabdocoela and its symbiotic group possesses a more rapidly evolving mitochondrial genome. ConclusionsThe mitochondrial genome of Craspedella pedum displays uncommon characteristics, combined extended branch lengths and elevated GORR, suggesting rapid evolution and extensive rearrangements. Our phylogenetic analysis, integrating additional mitogenome data, further corroborates the paraphyly of the Neoophora clade and offers novel insights into turbellarian phylogeny. For the first time, we confirmed the accelerated evolution of mitochondrial genomes in symbiotic tubellarians compared to free-living ones, as evidenced by a longer average Brl, a higher average GORR, and relaxed selection pressure. Additionally, with the same evidences, we found that Rhabdocoela also exhibited accelerated mitochondrial genome evolution in planarians.

genomics↗

bioRxiv2024

Mitochondrial DNA Release and Activation of the cGAS-STING Pathway in Lethal Stx12 Knockout Mice

STX12 (syntaxin12 or syntaxin13), a member of the SNARE protein family, plays a crucial role in intracellular vesicle transport and membrane fusion. Our previous research has demonstrated that Stx12 knockout mice exhibit perinatal lethality with iron deficiency anemia. Despite its importance, the comprehensive physiological and pathological mechanism of STX12 remain largely unknown. Here, we uncover that STX12 deficiency causes the depolarization of mitochondrial membrane potential in zebrafish embryos and mouse embryonic fibroblasts. Additionally, the loss of STX12 decreases levels of mitochondrial complex subunits, accompanying mitochondrial DNA (mtDNA) release and activating cGAS-STING pathway and Type I interferon pathway in the lung tissue of Stx12-/- mice. Additionally, we have observed a substantial increase in cytokines and neutrophil infiltration within the lung tissues of Stx12 knockout mice, indicating a severe inflammation, which could be a contributing factor for Stx12-/-mortality. Various interventions have failed to rescue the lethal phenotype, suggesting that systemic effects may contribute to lethality. Further research is warranted to elucidate potential intervention strategies. Overall, our findings uncover the critical role of STX12 in maintaining mitochondrial function and mtDNA stability in pulmonary cells, and reveal that STX12 depletion results in pulmonary mtDNA release and activates mtDNA-dependent innate immunity.

molecular biology↗

bioRxiv2022

Multi-omics integrated analysis reveals a specific phenotype of CD8+ T cell may contribute to immunothromosis via Th17 response in severe and critical COVID-19

T lymphocyte reduction and immunosenescence frequently occur in severe and critical coronavirus disease 2019 (COVID-19) patients, which may cause immunothrombosis and numerous sequelae. This study integrated analyzed multi-omics data from healthy donors, pneumonia, COVID-19 patients (mild & moderate, severe, and critical), and convalescences, including clinical, laboratory test, PBMC bulk RNA-seq, PBMC scRNA-seq and TCR-seq, BAL scRNA-seq, and lung proteome. We revealed that there are certain associations among T lymphocyte reduction, CD8+ T cell senescence, Th17 immune activation, and immunothrombosis. A specific phenotype (S. P.) CD8+ T cells were identified in severe and critical COVID-19 patients in both PBMC and BAL scRNA-seq, which showed highly TCR homology with terminal effector CD8+ T cells and senescent CD8+ T cells. Pseudotime analysis showed that the S. P. CD8+ T cells were located in the transition trajectory from mild to severe disease. Which may be activated by terminal effector CD8+ T cells or senescent CD8+ T cells, thereby promoting Th17 cell differentiation. This phenomenon was absent in healthy donors, mild and moderate COVID-19 patients, or convalescences. Our findings are an important reference for avoiding the conversion of patients with mild to severe diseases and provide insight into the future prevention and control of COVID-19 and its variants.

bioinformatics↗

bioRxiv2019

Mitochondrial architecture rearrangements produce asymmetrical nonadaptive mutational pressures that subvert the phylogenetic reconstruction in Isopoda

The phylogeny of Isopoda, a speciose order of crustaceans, remains unresolved, with different datasets often producing starkly incongruent phylogenetic hypotheses. We hypothesised that extreme diversity in their life histories might be causing compositional heterogeneity/heterotachy in their mitochondrial genomes, and compromising the phylogenetic reconstruction. We tested the effects of different datasets (mitochondrial, nuclear, nucleotides, amino acids, concatenated genes, individual genes, gene orders), phylogenetic algorithms (assuming data homogeneity, heterogeneity, and heterotachy), and partitioning; and found that almost all of them produced unique topologies. As we also found that mitogenomes of Asellota and two Cymothoida families (Cymothoidae and Corallanidae) possess inversed base (GC) skew patterns in comparison to other isopods, we concluded that inverted skews cause long-branch attraction phylogenetic artefacts between these taxa. These asymmetrical skews are most likely driven by multiple independent inversions of origin of replication (i.e., nonadaptive mutational pressures). Although the PhyloBayes CAT-GTR algorithm managed to attenuate some of these artefacts (and outperform partitioning), mitochondrial data have limited applicability for reconstructing the phylogeny of Isopoda. Regardless of this, our analyses allowed us to propose solutions to some unresolved phylogenetic debates, and support Asellota are the most likely candidate for the basal isopod branch. As our findings show that architectural rearrangements can produce major compositional biases even on short evolutionary timescales, the implications are that proving the suitability of data via composition skew analyses should be a prerequisite for every study that aims to use mitochondrial data for phylogenetic reconstruction, even among closely related taxa.

evolutionary biology↗

bioRxiv2018

Maize EHD1 is Required for Kernel Development and Vegetative Growth through Regulating Auxin Homeostasis

The roles of EHDs in clathrin-mediated endocytosis (CME) in plants are poorly understood. Here, we isolated a maize mutant, designated as ehd1, which showed defects in kernel development and vegetative growth. Positional cloning and transgenic analysis revealed that ehd1 encodes an EHD protein. Internalization of the endocytic tracer FM4-64 was significantly reduced in ehd1 mutant and ZmEHD1 knock-out mutants. We further demonstrated that ZmEHD1 and ZmAP2 {sigma} subunit physically interact in the plasma membranes. Cellular IAA levels were significantly lower in ehd1 mutant than in wild-type maize. Auxin distribution and ZmPIN1a-YFP localization were altered in ehd1 mutant. Exogenous application of 1-NAA but not GA3 rescued the seed germination and seedling emergency phenotypic defects of ehd1 mutants. Taken together, these results indicate that ZmEHD1 regulates auxin homeostasis by mediating CME through its interaction with the ZmAP2 {sigma} subunit, which is crucial for kernel development and vegetative growth of maize.

plant biology↗

bioRxiv2017

Anti-HIV activity prediction and enrichment identify novel human targets for Anti-HIV therapy

Human immunodeficiency virus (HIV) relies heavily on the host proteins to facilitate its entry and replication. Currently, more than 4000 human proteins are recorded to be involved in the HIV-1 life cycle. Identifying appropriate anti-HIV targets from so many host proteins is crucial to anti-HIV drug development, but a challenging work. Here we combined anti-HIV activity prediction and enrichment analysis to identify novel human targets for anti-HIV therapy. We firstly developed an accurate prediction tool named Anti-HIV-Predictor (AUC>0.96) to predict the anti-HIV activity of given compounds. Using this tool, we predicted 10488 anti-HIV compounds from ChEMBLdb. Then, based on this result and relationships of targets and compounds, we inferred 73 anti-HIV targets that enriched with anti-HIV compounds. The functional annotation and network analysis revealed that they directly or indirectly interact with 20 HIV proteins through neuropeptide signaling, GPCR signaling, cell surface signaling pathway, and so on. Nearly half of these targets overlap with the NCBI HIV dataset. However, the percentage of known therapeutic targets in these targets is significantly higher than that in the NCBI HIV dataset. After a series of feature analysis, we identified 13 novel human targets with high potential as anti-HIV targets, the inhibitors of which have experimentally confirmed anti-HIV activity. It is noteworthy that the inhibitors of REN and CALCA have better anti-HIV activity than CCR5 inhibitors. Taken together, our findings provide novel human targets for the host-oriented anti-HIV drug development and should significantly advance current anti-HIV research.

bioinformatics↗

bioRxiv2016

Efficient repositioning of approved drugs as anti-HIV agents using Anti-HIV-Predictor

Development of new, effective and affordable drugs against HIV is urgently needed. In this study, we developed a worlds first web server called Anti-HIV-Predictor (http://bsb.kiz.ac.cn:70/hivpre) for predicting anti-HIV activity of given compounds. This server is rapid and accurate (accuracy >93% and AUC > 0.958). We applied the server to screen 1835 approved drugs for anti-HIV therapy. Totally 67 drugs were predicted to have anti-HIV activity, 25 of which are anti-HIV drugs. Then we experimentally evaluated 35 predicted new anti-HIV compounds by assays of syncytia formation, p24 quantification, cytotoxicity. Finally, we repurposed 7 approved drugs (cetrorelix, dalbavancin, daunorubicin, doxorubicin, epirubicin, idarubicin and valrubicin) as new anti-HIV agents. The original indication of these drugs is involved in a variety of diseases such as female infertility and cancer. Anti-HIV-Predictor and the 7 repurposed anti-HIV agents provided here demonstrate the efficacy of this strategy for discovery of new anti-HIV agents.

bioinformatics↗