Biology subjects

sun, j.

Publications and source records attributed to sun, j..

10 recordsLinked to original sources

bioRxiv2026

Ex vivo human airway epithelia modelling reveals specific alterations in lung and hematopoietic stem cell transplant recipients

Deterioration of lung function is a major cause of long-term morbidity after hematopoietic stem cell transplantation (HSCT) and lung transplantation (LT). In both settings, obliterative bronchiolitis represents the most common final pathway, with bronchiolitis obliterans syndrome (BOS), representing its clinical correlate. Understanding of the pathophysiological mechanisms leading to BOS is limited by restricted access to human lung tissue and the imperfect relevance of animal models. We hypothesize that transplantation procedures cause bronchial epithelial damage that promotes the development of BOS. To investigate this, we established ex vivo human airway epithelia (HAE) cultures from bronchial biopsies of HSCT and LT recipients, collected prior to the development of BOS, and compared them with non-transplant controls. HAE from HSCT recipients exhibited reduced tissue differentiation ability, associated with defect in mucociliary clearance and impaired barrier integrity, most markedly in one patient who subsequently developed BOS. In contrast, LT-derived HAE showed normal mucociliary clearance and barrier integrity but displayed increased mucin secretion. Donor and recipient-derived cells were detected in both paraffin-embedded biopsies and reconstructed HAE derived from transplant recipients, demonstrating epithelial chimerism. Our data highlight specific modifications of the airway epithelium after LT and HSCT that may represent a first trigger for subsequent BOS development.

Molecular Biology↗

bioRxiv2025

16S rRNA Survey Reveals the Potential of Oral Microbiota in Distinguishing Patients with Chronic Heart Failure from Healthy Controls

BackgroundOral microbiota can reflect physiological functions and pathological conditions in human body. Patients with chronic heart failure (CHF) exhibit distinct oral health status compared to healthy controls (HCs), which is attributed to the differences in dominant microbial communities present in the oral cavity. Up to date, there are few studies examined the association between CHF and dominant oral microbiota. To fill in this research gap, this study aimed to investigate the differences of oral microbiota between CHF patients and HCs, to identify valuable novel biomarkers for CHF. MethodsChronic heart failure patients and healthy volunteers were recruited. Oral microbiota samples were then collected using oral swabs, and 16S rRNA sequencing was employed to analyze the microbiota. Statistical analysis was conducted to identify key bacteria at multiple taxonomic levels in the oral microbiota samples from both the CHF patient and healthy control groups, with a focus on core genera to identify potential biomarkers and evaluate their diagnostic efficacy. ResultsThere were 60 CHF patients and 30 HCs were recruited, with 42 CHF patients with New York Heart Association (NYHA) functional class II-IV and 28 HCs were included in the final analysis. The alpha diversity was higher in HCs, while beta diversity was higher in CHF patients. The CHF patients showed significant differences from HCs at five gene (phylum, class, order, family and genus) levels by analyzing the relative richness of microbiota at different taxomal levels. Altogether 14 microbes could distinguish CHF patients from HCs, i.e., Abiotrophia, Butyrivibrio, Lactobacillus, Capnocytophaga and Neisseria which are more abundant in CHF patients, and Actinomyces, Anaerovorax, Eubacterium, Kingella, Mogibacterium, Peptococcus, Peptostreptococcus, Solobacterium and TM7_genus_incertae_sedis which are more abundant in HCs. Furthermore, the AUC of their combined diagnosis was 83.7% (95% confidential interval 74.1%-93.3%), which have high reliability for the diagnostic significance. In accordance to Spearmans correlation, Eubacterium, Solobacterium and Rhizobium were core genera and the abundance of Eubacterium and Solobacterium exhibited downward trends as NYHA class increases. ConclusionThis study revealed the dysbiosis of the oral microbiota in CHF patients and identified potential biomarkers for CHF diagnosis and management. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/669863v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@d60f6eorg.highwire.dtl.DTLVardef@18f17ceorg.highwire.dtl.DTLVardef@163f0daorg.highwire.dtl.DTLVardef@599bcd_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

KIF18A in HCC Metastasis: Dual Role in Anoikis Resistance and Chromosome Instability

The study explores the role of KIF18A, a gene linked to whole-genome doubling (WGD) and chromosomal instability (CIN), in the metastatic progression of hepatocellular carcinoma (HCC). We found that KIF18A is a critical link between CIN and anoikis resistance, key factors in HCC metastasis. Through the bulk-seq analysis, we identified the pressures of anoikis and CIN faced by tumor cells during HCC metastasis and identified hub genes central to this process. Our results reveal that E2F activation during HCC progression leads to the transcription of KIF18A, promoting the survival and metastasis of CIN tumors. Overexpression of KIF18A leads to longer tumor life, more micronuclei, and increased survival and metastasis through non-canonical NF-kB activation. Deletion of KIF18A stabilizes the nuclear membrane of the micronucleus, silences cGAS-STING and PI3K-AKT pathways, and inhibits classical NF-kB. The studys limitations include the need for further animal studies to validate the findings and explore the transient activation of the cGAS-STING pathway. Additionally, future research could focus on the potential therapeutic implications of targeting KIF18A in cancer treatment.

cancer biology↗

bioRxiv2024

Screening for metastasis-related genes in mouse melanoma cells through sequential tail vein injection

Tumor metastasis, responsible for approximately 90% of cancer-associated mortality, remains poorly understood. Here in this study we employed a melanoma lung metastasis model to screen for metastasis-related genes. By sequential tail vein injection of mouse melanoma B16F10 cells and the subsequently derived cells from lung metastasis into BALB/c mice, we successfully obtained highly metastatic B16F15 cells after five rounds of in vivo screening. RNA-sequencing analysis of B16F15 and B16F10 cells revealed a number of differentially expressed genes, some of these genes have previously been associated with tumor metastasis while others are novel discoveries. The identification of these metastasis-related genes not only improve our understanding of the metastasis mechanisms, but also provide potential diagnostic biomarkers and therapeutic targets for metastatic melanoma.

cell biology↗

bioRxiv2023

The mitochondrial deoxyguanosine kinase is required for female fertility in mice

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleoside in the mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. We found that Dguok knockout results in female infertility. Mechanistically, the deficiency of DGUOK hinders ovarian development and oocyte maturation. Moreover, Dguok deficiency in oocytes caused a significant reduction in mitochondrial DNA and abnormal mitochondrial dynamics, and impaired germinal vesicle breakdown. Only few DGUOK-deficient oocytes were able to extrude the first polar body during in vitro maturation, and these oocytes showed irregular chromosome arrangement and different spindle lengths. In addition, Dguok deficiency elevated reactive oxygen species and accelerated apoptosis in oocytes. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate that DGUOK is a potential marker for the diagnosis of female infertility.

cell biology↗

bioRxiv2022

Single-cell RNA sequencing reveals dysregulation of spinal cord cell types in a several spinal muscular atrophy mouse model

Although spinal muscular atrophy (SMA) is a motor neuron disease caused by the loss of survival of motor neuron (SMN) proteins, there is growing evidence that non-neuronal cells play important roles in SMA pathogenesis. However, transcriptome alterations occurring at the single-cell level in SMA spinal cord remain unknown, preventing us from fully comprehending the role of specific cells. Here, we performed single-cell RNA sequencing of the spinal cord of a severe SMA mouse model, and identified ten cell types as well as their differentially expressed genes. Using CellChat, we found that cellular communication between different cell types in the spinal cord of SMA mice was significantly reduced. A dimensionality reduction analysis revealed 29 cell subtypes and their differentially expressed gene. A subpopulation of vascular fibroblasts showed the most significant change in the SMA spinal cord at the single-cell level. This subpopulation was drastically reduced, possibly causing vascular defects and resulting in widespread protein synthesis and energy metabolism reductions in SMA mice. This study reveals for the first time a single-cell atlas of the spinal cord of mice with severe SMA, and sheds new light on the pathogenesis of SMA.

neuroscience↗

bioRxiv2021

Heterogeneity and molecular programming of progenitors for motor neurons and oligodendrocytes

The pMN domain is a restricted domain in the ventral spinal cords, defined by the expression of olig2 gene. The fate determination of pMN progenitors is highly temporally and spatially regulated, with motor neurons and oligodendrocyte progenitor cells (OPCs) developing sequentially. Insight into the heterogeneity and molecular programs of pMN progenitors is currently lacking. With the zebrafish model, we identified multiple states of neural progenitors using single-cell sequencing: proliferating progenitors, common progenitors for both motor neurons and OPCs, and restricted precursors for either motor neurons or OPCs. We found specific molecular programs for neural progenitor fate transition, and manipulations of representative genes in the motor neuron or OPC lineage confirmed their critical role in cell fate determination. The transcription factor NPAS3 is necessary for the development of the OPC lineage and can interact with many known genes associated with schizophrenia. Deciphering progenitor heterogeneity and molecular mechanisms for these transitions will elucidate the formation of complex neuron-glia networks in the central nervous system during development, and understand the basis of neurodevelopmental disorders.

neuroscience↗

bioRxiv2020

Prediction of LncRNA Encoded Small Peptides inGlioma and The Oligomer Channel Functional AnalysisUsing in Silico Approaches

Glioma is lethal malignant brain cancers, many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating glioma proliferation, migration, apoptosis and differentiation. Recently, new studies have suggested that some long noncoding RNAs (lncRNAs) containing small open reading frames (smORFs), can encode small peptides and form oligomers for water or ion regulation. However, because these peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatic methods and softwares to identify and evaluate lncRNAs in gliomas that may encode small transmembrane peptides. Combining ab initio homology modeling, molecular dynamics simulations and energetic calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs. We found that one key hub lncRNA, DLEU1, which contains two smORFs (ORF1 and ORF8) could encode small peptides that form pentameric channels. The mechanics of water and ion (Na + and Cl-) transport through this pentameric channel were simulated. The potential of mean force (PMF) of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 neither permeating ions nor water. This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, it provides a theoretical basis for drug development.

biophysics↗

bioRxiv2020

The roles of wrinkle structures in the veins of Asian Ladybird and bioinspiration

The deployable hind wings of the Asian ladybird beetle (Harmonia axyridis) play important roles in their flight. Wrinkle structures of veins are found on the bending zones of the hind wings of H. axyridis. This paper investigates the effect of the wrinkle structures of the veins of the hind wing on its deformation. Based on the nanomechanical properties of the veins, morphology of the hind wing, surface structures of veins and microstructures of the cross sections, including the veins and wing membranes, we establish four three-dimensional coupling models for hind wings with/without wrinkles with different and uniform reduced modulus. Relative to the bending and twisting model shapes, Model I, which includes the wrinkle structure and different reduced-modulus veins, has much more flexibility of passive deformation to control wing deformations. The results show that both the wrinkle structures in the bending zone and varying reduced modulus of the veins contribute to the flight performance of bending and twisting deformations of the hind wings, which have important implications for the bionic design of the biomimetic deployable wing of micro air vehicles (MAVs).

biophysics↗

bioRxiv2018

Single-cell level transcriptome of the maize pathogenic fungi cochliobolus heterostrophus race O in infection reveal the virulence related genes, and potential circRNA effector

Cochliobolus heterostrophus is a crucial pathogenic fungus that causes southern corn leaf blight (SCLB) in maize worldwide, however, the virulence mechanism of the dominant race O remains unclear. In this report, the single-cell level of pathogen tissue at three infection stages were collected from the host interaction-situ, and were performed next-generation sequencing from the perspectives of mRNA, circular RNA(circRNA) and long noncoding RNA(lncRNA). In the mRNA section, signal transduction, kinase, oxidoreductase, and hydrolase, et al. were significantly related in both differential expression and co-expression between virulence differential race O strains. The expression pattern of the traditional virulence factors nonribosomal peptide synthetases (NPSs), polyketide synthases (PKSs) and small secreted proteins (SSPs) were multifarious. In the noncoding RNA section, a total of 2279 circRNAs and 169 lncRNAs were acquired. Noncoding RNAs exhibited differential expression at three stages. The high virulence strain DY transcribed 450 more circRNAs than low virulence strain WF. Informatics analysis revealed numbers of circRNAs which positively correlate with race O virulence, and a cross-kingdom interaction between the pathogenic circRNA and host miRNA was predicted. An important exon-intron circRNA Che-cirC2410 combines informatics characteristics above, and highly expressed in the DY strain. Che-cirC2410 initiate from the pseudogene chhtt, which doesnt translate genetic code into protein. In-situ hybridization tells the sub-cellular localization of Che-cirC2410 include pathogen`s mycelium, periplasm, and the diseased host tissues. The target of Che-cirC2410 was predicted to be zma-miR399e-5P, and the interaction between noncoding RNAs was proved. More, the expression of zma-miR399e-5P exhibited a negative correlation to Che-cirC2410 in vivo. The deficiency of Che-circ2410 decreased the race O virulence. The host resistance to SCLB was weakened when zma-miR399e-5P was silenced. Thus, a novel circRNA-type effector and its resistance related miRNA target are proposed cautiously in this report. These findings enriched the pathogen-host dialogue by using noncoding RNAs as language, and revealed a new perspective for understanding the virulence of race O, which may provide valuable strategy of maize breeding for disease resistance.\n\nAuthor SummaryThe southern corn leaf blight (caused by Cochliobolus heterostrophus) is not optimistic in Asia, however we have limit knowledge about the infection mechanism of the dominant C.heterostrophus race O. We take full advantage of the ideal C.heterostrophus genome database, laser capture microdissection and single-cell level RNA sequencing. Hence, we could avert the artificial influence such as medium, and profile the real gene mobilization strategy in the infection. The results of coding RNA section were accessible, virulence related genes (such as the signal transduction, PKS, SSP) were detected in RNA-seq,which accord with previous reports. However, the results of noncoding RNA was astonished, 2279 circular RNAs (circRNA) and 169 long noncoding RNAs (lncRNA) were revealed in our results. Generally, the function of noncoding RNA was hypothesized in single species, but we boldly guess that the function of circRNA is rather complicated in the pathogen-host interaction. Finally, the circRNA in-situ hybridization (ISH) demonstrate the secretion of pathogen circRNA into the host tissue. By bioinformatic prediction, we found a sole microRNA target, and proved the interaction between circRNA and microRNA. These findings are likely to reveal a novel pathogen effector type: secreted circRNA.

microbiology↗