Biology subjects

JIA, Y.

Publications and source records attributed to JIA, Y..

5 recordsLinked to original sources

bioRxiv2025

Characterization of the Mechanisms Underlying Sulfasalazine-Induced Ferroptotic Cell Death: Role of Protein Disulfide Isomerase-Mediated NOS Activation and NO Accumulation

Sulfasalazine (SAS), a clinically-utilized anti-inflammatory drug, has been shown to induce ferroptosis by inhibiting system Xc- activity, thereby causing cellular glutathione depletion. Recently, it was shown that protein disulfide isomerase (PDI) is an upstream mediator of oxidative cell death (oxytosis/ferroptosis) induced by glutamate, erastin, RSL3 and SAS. The present study aims to further characterize the detailed biochemical and cellular mechanisms of SAS-induced ferroptosis in two cell lines, i.e., H9C2 rat cardiomyocytes and BRL-3A rat hepatocytes, focusing on elucidating the critical role of PDI in mediating SAS-induced toxicity. We find that SAS can induce ferroptosis in H9C2 and BRL-3A cells, which is accompanied by a sequential increase in the buildup of cellular nitric oxide (NO), reactive oxygen species (ROS) and lipid-ROS. SAS activates PDI-mediated dimerization of the inducible NO synthase (iNOS) and cellular NO accumulation, and these effects are followed by ROS and lipid-ROS accumulation. Furthermore, SAS markedly upregulates the expression of iNOS protein in these cells. Knockdown of PDI or pharmacological inhibition of its catalytic activity each effectively suppresses SAS-induced iNOS dimerization, along with abrogation of SAS-induced accumulation of NO, ROS and lipid-ROS, and prevention of ferroptosis. On the other hand, PDI activation through the use of TrxR1 inhibitors sensitizes these cells to SAS-induced ferroptosis. These experimental findings provide further experimental support for a pivotal role of PDI in SAS-induced cytotoxicity through the activation of the PDI-NOS-NO axis, which then leads to cellular ROS and lipid-ROS accumulation, and ultimately induction of oxidative cell death.

biochemistry↗

bioRxiv2025

Highly heterozygous Citrus changshan-huyou Y. B. Chang originated from ancient hybridization between mandarin and pummelo and displayed distinct tissue-specific allelic imbalance

The genus Citrus is characterized by a reticulate evolutionary history with frequent hybridization, making it an intriguing subject for genome evolution investigation. Citrus changshan Y. B. Chang (Huyou) is a unique landrace first discovered in Zhejiang Province, China with premium fruit quality. The evolutionary origin of Huyou has puzzled local botanists and growers. Here, we sequenced a 120-years-old "ancestral tree" of Huyou using PacBio long read and Hi-C sequencing and assembled 2 high-quality haplotype-resolved genomes HY1 and HY2. Huyou displayed a genome heterozygosity level at 3.07%, among the highest in published citrus genomes. Using a k-mer-based tracing approach, we explicitly resolved that HY1 genome contained 87.8% mandarin, 7.3% pummelo, 0.2% citron origin, whereas HY2 had 85.0% pummelo, 2.9% mandarin, 0.3% citron, implying a hybridization event between mandarin and pummelo. Phylogeny dating showed that HY1 (2.0 Mya) and HY2 (2.18 Mya) had diverged earlier than the split of Citrus clementina and Citrus reticulata, and the split of Citrus grandis and Citrus maxima, respectively. We observed clear chromosomal recombination on chr8 and chr9 in HY1, which may have occurred after the ancestral hybridization. Further transcriptome analyses in 6 tissues revealed a strong allelic dominance of HY2 over HY1 in root tissue and moderately in stem, leaf, flower, and fruits. KEGG enrichment analyses revealed that genes related to antioxidants biosynthesis and lipid metabolisms were most significantly affected by allelic imbalance. This first report of allelic imbalance in citrus species support Huyou as an interesting model to investigate genome evolution following distant hybridization.

evolutionary biology↗

bioRxiv2024

A pangenome and pantranscriptome of hexaploid oat

Oat grain is a traditional human food rich in dietary fiber that contributes to improved human health. Interest in the crop has surged in recent years owing to its use as the basis for plant-based milk analogs. Oat is an allohexaploid with a large, repeat-rich genome that was shaped by subgenome exchanges over evolutionary timescales. In contrast to many other cereal species, genomic research in oat is still at an early stage, and surveys of structural genome diversity and gene expression variability are scarce. Here, we present annotated chromosome-scale sequence assemblies of 33 wild and domesticated oats along with an atlas of gene expression across six tissues of different developmental stages in 23 accessions. We describe the interplay of gene expression diversity across subgenomes, accessions and tissues. Gene loss in the hexaploid is accompanied by compensatory up-regulation of the remaining homeologs, but this process is constrained by subgenome divergence. Chromosomal rearrangements have significantly impacted recent oat breeding. A large pericentric inversion associated with early flowering explains distorted segregation on chromosome 7D and a homeologous sequence exchange between chromosomes 2A and 2C in a semidwarf mutant has risen to prominence in Australian elite varieties. The oat pangeome will promote the adoption of genomic approaches to understanding the evolution and adaptation of domesticated oats and will accelerate their improvement.

genomics↗

bioRxiv2020

Genome-wide identification and transcriptional analyses of MATE transporter genes in root tips of wild Cicer spp. under aluminium stress

Chickpea is an economically important legume crop with high nutritional value in human diets. Aluminium-toxicity poses a significant challenge for the yield improvement of this increasingly popular crop in acidic soils. The wild progenitors of chickpea may provide a more diverse gene pool for Al-tolerance in chickpea breeding. However, the genetic basis of Al-tolerance in chickpea and its wild relatives remains largely unknown. Here, we assessed the Al-tolerance of six selected wild Cicer accessions by measuring the root elongation in solution culture under control (0 {micro}M Al3+) and Al-treatment (30 {micro}M Al3+) conditions. Al-treatment significantly reduced the root elongation in all target lines compared to the control condition after 2-days growth. However, the relative reduction of root elongation in different lines varied greatly: 3 lines still retained significant root growth under Al-treatment, whilst another 2 lines displayed no root growth at all. We performed genome-wide identification of multidrug and toxic compound extrusion (MATE) encoding genes in the Cicer genome. A total of 56 annotated MATE genes were identified, which divided into 4 major phylogeny groups (G1-4). Four homologues to lupin LaMATE (> 50% aa identity; named CaMATE1-4) were clustered with previously characterised MATEs related to Al-tolerance in various other plants. qRT-PCR showed that CaMATE2 transcription in root tips was significantly up-regulated upon Al-treatment in all target lines, whilst CaMATE1 was up-regulated in all lines except Bari2_074 and Deste_064, which coincided with the lines displaying no root growth under Al-treatment. Transcriptional profiling in five Cicer tissues revealed that CaMATE1 is specifically transcribed in the root tissue, further supporting its role in Al-detoxification in roots. This first identification of MATE-encoding genes associated with Al-tolerance in Cicer paves the ways for future functional characterization of MATE genes in Cicer spp., and to facilitate future design of gene-specific markers for Al-tolerant line selection in chickpea breeding programs.

plant biology↗

bioRxiv2020

Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity

Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a receptor binding domain mutation that leads to weaker ACE2 binding capability based on in silico simulation, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and requires attention from researchers working on vaccine development around the world. HighlightsO_LIBased on the currently available genome sequence data, we provided direct genetic evidence that the SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. C_LIO_LIThe spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. C_LIO_LIMinimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. C_LIO_LIWe confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. C_LIO_LIWe provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. C_LI

evolutionary biology↗