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Biology subjects

Liu, X.-L.

Publications and source records attributed to Liu, X.-L..

6 recordsLinked to original sources

ArchLips: A comprehensive in silico database for high-throughput identification of archaeal lipids

Archaeal membrane lipids are markedly distinct from those in bacteria and eukaryotes, serving as unique biomarkers for unraveling their ecological and biogeochemical roles. Recent advancements in lipidomics have facilitated detailed cellular-level characterizations of lipid compounds. However, the lack of a comprehensive and dedicated database has severely limited large-scale, high-throughput investigations of archaeal lipids. We present ArchLips, a comprehensive database containing 218,868 in silico molecular structures and tandem mass spectra of 199,248 corresponding archaeal lipids. ArchLips enables the rapid and accurate identification of characterized archaeal lipid compounds from both pure cultures and environmental samples, serving as a transformative tool for enhancing our understanding of archaeal diversity and their ecological and evolutionary significance within global ecosystems.

biochemistry↗

Physiological, transcriptomic and metabolomic responses of the marine diatom Phaeodactylum tricornutum to auxin

Auxin, an essential phytohormone, is widely used to promote plant growth and development. However, the effect of auxin on diatoms and its mechanism remain underexplored. Here, we studied the impact of auxin 3-indoleacetic acid (IAA) on the marine diatom Phaeodactylum tricornutum and the underlying molecular mechanisms. We found that 5 g L-1 of IAA promotes the growth of P. tricornutum in a time- dependent manner. Treatment with IAA resulted in significant changes in photosynthetic pigments and malondialdehyde, chlorophyll fluorescence, and antioxidant enzyme activities. In addition, transcriptomics showed that IAA exposure leads to upregulation of a large number of differential genes (DEGs) in carbon fixation and porphyrin metabolism, several of which were verified by qPCR. Furthermore, corresponding metabolites of these pathways were also validated by metabolomic analysis. Thus, IAA exhibits growth-promotion effect on the diatom mainly through increasing photosynthetic carbon sequestration and the expression of genes in porphyrin synthesis. Our results provide key data on the action mechanism of IAA in promoting the growth of a diatom.

plant biology↗

Biosynthesis of H-GDGTs linked to ocean oxygen deficiency

Archaeal membrane lipids GDGTs (glycerol dialkyl glycerol tetraethers) are biomarkers used for tracking Earths historical environmental changes. Among these GDGTs, the H-shaped GDGTs (H-GDGTs, or GMGTs) represent a less-explored and often overlooked subset, with its biosynthetic pathway and geological significance remaining elusive. Here, we identified the gene responsible for biosynthesizing H-GDGTs, which encodes to a radical S-adenosyl-L-methionine (SAM) enzyme, named as H-GDGTs bridge synthase (Hbs). Heterologous expression of the gene hbs in a methanogen, as well as in vitro activity assay using the purified Hbs enzyme were performed. Additionally, we found that the genes encoding Hbs are exclusively present in obligate anaerobic archaea genomes and the metagenomes obtained from oxygen-deficient environments, but not in oxic settings. The H-GDGTs lipids were also consistently enriched in the modern oxygen-deficient environments, and remarkably accumulated in ancient sediments during oceanic anoxic event-2 (OAE-2, [~]94 million years ago) period. Our findings indicate H-GDGTs holds significant promise as a novel biomarker for studying historical ocean oxygen deficiency supported by a well-established biological basis.

microbiology↗

Rapid and accurate multi-phenotype imputation for millions of individuals

Deep phenotyping can enhance the power of genetic analysis, including genome-wide association studies (GWAS), but the occurrence of missing phenotypes compromises the potential of such resources. Although many phenotypic imputation methods have been developed, the accurate imputation of millions of individuals remains extremely challenging. In the present study, we developed a novel multi-phenotype imputation method based on mixed fast random forest (PIXANT) by leveraging efficient machine learning (ML)-based algorithms. We demonstrate that PIXANT runtime is faster and computer memory usage is less than that of other state-of-the-art methods when applied to the UK Biobank (UKB) data, suggesting that PIXANT is scalable to cohorts with millions of individuals. Our simulations with hundreds of individuals showed that PIXANT accuracy was superior to or comparable to the accuracy of the most advanced methods available. PIXANT was used to impute 425 phenotypes for the UKB data of 277,301 unrelated White British citizens. When GWAS was subsequently performed on the imputed phenotypes, 18.4% more GWAS loci were identified than before imputation (8,710 vs 7,355). The increased statistical power of GWAS identified novel positional candidate genes affecting heart rate, such as RNF220, SCN10A, and RGS6, suggesting that the use of imputed phenotype data from a large cohort may lead to the discovery of novel genes for complex traits.

bioinformatics↗

Quantitative Analysis of Tissue Secretome Reveals the Diagnostic and Prognostic Value of Carbonic Anhydrase II in Hepatocellular Carcinoma

Early detection and intervention are key strategies to reduce mortality, increase long-term survival and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ) quantitative proteomic strategy was used to study the secretome in conditioned media from HCC cancerous tissues, surrounding noncancerous and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 secretory proteins were identified to be dysregulated in the cancerous and surrounding noncancerous tissues compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients than that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence (TTR) and overall survival (OS). Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition (EMT) pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis and provides a valuable resource of the HCC secretome for investigating serological biomarkers.

cancer biology↗

Circular RNAs regulate cancer stem cells by FMRP against CCAR1 complex in hepatocellular carcinoma

Circular RNA (circRNA) possesses great pre-clinical diagnostic and therapeutic potentials in multiple cancers. However, the underlying correlation between circRNAs and cancer stem cells (CSCs) has not been reported. The absence of circZKSCAN1 endowed several malignant properties including cancer stemness and tightly correlated with worse overall and recurrence-free survival rate in HCC cells in vitro and in vivo. Bioinformatics analysis and RNA immunoprecipitation-sequencing (RIP-seq) results revealed that circZKSCAN1 exerted its inhibitive role by competitively binding FMRP, therefore, block the binding between FMRP and {beta}-catenin-binding protein-cell cycle and apoptosis regulator 1 (CCAR1) mRNA, and subsequently restraining the transcriptional activity of Wnt signaling. In addition, RNA-splicing protein Quaking 5 was found downregulated in HCC tissues and responsible for the reduction of circZKSCAN1. Collectively, this study revealed the mechanisms underlying the regulatory role of circZKSCAN1 in HCC CSCs and identified the newly discovered Qki5- circZKSCAN1-FMRP-CCAR1-Wnt signaling axis as a potentially important therapeutic target for HCC treatment.\n\nStatement of significanceO_LICircZKSCAN1, a novel negative regulator for cancer stem cells, was firstly identified with reverse correlation with HCC prognosis.\nC_LIO_LICircZKSCAN1 directly targets FMRP, and competitive binding with {beta}-catenin-binding protein cell cycle and apoptosis regulator 1 (CCAR1) for its activity.\nC_LIO_LIThe decreased expression of Quaking 5 is responsible for the absence of circZKSCAN1 in HCC.\nC_LI

cancer biology↗