Biology subjects

Yue, B.

Publications and source records attributed to Yue, B..

8 recordsLinked to original sources

bioRxiv2025

Nanopore Sequencing Unveils Somatic Structural Variations as Biomarkers in Laryngeal squamous cell carcinoma Genomes

Laryngeal squamous cell carcinoma (LSCC) is an aggressive cancer with poor quality of life, largely due to the absence of reliable molecular biomarkers for early diagnosis and prognosis. While somatic structural variations (SVs) have been documented in LSCC, conventional short-read sequencing approaches are inherently limited in detecting of large-scale somatic SVs, which are critical to understanding tumorigenesis. Here, we presented SomaGauss-SV, a somatic SVs detection workflow leveraging nanopore long-read sequencing data. Benchmarking against five paired tumor cell line datasets showed SomaGauss-SV consistently achieves a balanced high precision and recall. SomaGauss-SV applied to 15 paired LSCC tumor-blood samples uncovered a comprehensive SVs landscape and a significant positive correlation between somatic deletion burden and smoking intensity. Furthermore, a high-frequency somatic simple repeat expansion was identified in 20/27 (74.1%) of LSCC patients, upregulating the expression of genes TP53BP2 and FBXO28 through spatial proximity. These findings underscore the potential of long-read sequencing and SomaGauss-SV in uncovering previously unexplored genomic rearrangements in LSCC, providing valuable resources for biomarker discovery.

bioinformatics↗

bioRxiv2024

Multi-omics investigation of spontaneous T2DM macaque reveals gut microbiota promote T2DM by up-regulating the absorption of excess palmitic acid

Although gut microbiota and lipid metabolites have been suggested to be closely associated with type 2 diabetes mellitus (T2DM), the interactions between gut microbiota, lipid metabolites and the host in T2DM development remains unclear. Rhesus macaques may be the best animal model to investigate these relationships given their spontaneous development of T2DM. We identified eight spontaneous T2DM macaques and conducted a comprehensive study investigating the relationships using multi-omics sequencing technology. Our results from 16S rRNA, metagenome, metabolome and transcriptome analyses identified that gut microbiota imbalance, tryptophan metabolism and fatty acid {beta} oxidation disorders, long-chain fatty acid (LCFA) accumulation, and inflammation occurred in T2DM macaques. We verified the accumulation of palmitic acid (PA) and activation of inflammation in T2DM macaques. Importantly, mice transplanted with spontaneous T2DM macaque fecal microbiota and fed a high PA diet developed prediabetes within 120 days. We determined that gut microbiota mediated the absorption of excess PA in the ileum, resulting in the accumulation of PA in the serum consequently leading to T2DM in mice. In particular, we demonstrated that the specific microbiota composition was probably involved in the process. This study provides new insight into interactions between microbiota and metabolites and confirms causative effect of gut microbiota on T2DM development.

microbiology↗

bioRxiv2024

Integrative phylogenetic analysis of the genus Episoriculus (Mammalia: Eulipotyphla: Soricidae)

Shrews in the genus Episoriculus are among the least-known mammals in China, where representatives occur mainly in the Himalayan and Hengduan mountains. We sequence one mitochondrial and three nuclear genes from 77 individuals referable to this genus, collect morphometric data for five shape and 11 skull measurements from 56 specimens, and use museum collections and GenBank sequences to analyze phylogenetic relationships between this and related genera in an integrated molecular and morphometric approach. Whereas historically anywhere from two to eight species have been recognized in this genus, we conclude that six (E. baileyi, E. caudatus, E. leucops, E. macrurus, E. sacratus, E. soluensis) are valid. We dissent from recent systematic reviews of this genus and regard E. sacratus to be a valid taxon, E. umbrinus to be a subspecies of E. caudatus, and transfer E. fumidus to Pseudosoriculus. Our record of E. soluensis is the first for China, and expands the previously recognized distribution of this taxon from Nepal and NE India into the adjacent Yadong and Nyalam counties. One further undescribed Episoriculus taxon may exist in Tibet.

zoology↗

bioRxiv2023

Lymphotoxin-β Promotes Bone Colonization and Osteolytic Outgrowth of Indolent Bone Metastatic cells of Breast Cancer

Bone metastatic relapse is a lethal consequence of breast cancer, occurring years after initial diagnosis. By analyzing single-cell transcriptomes of bone-seeding tumor cells and in vivo barcoded cDNA library screening, LT{beta} (lymphotoxin-{beta}) is identified as a key factor highly expressed in early-stage bone metastatic cells, associated with poor bone metastasis-free survival, and capable of promoting dormancy reactivation in multiple breast cancer models. Mechanistically, tumor-derived LT{beta} activates NF-{kappa}B2 signaling in osteoblasts to express CCL2/5, facilitating tumor cell seeding and accelerating osteoclastogenesis. Both processes contribute to the reactivation of dormancy and metastatic outgrowth. Blocking LT{beta} signaling with a decoy receptor significantly suppressed bone colonization and metastatic progression, whereas clinical sample analysis revealed significantly higher LT{beta} expression in bone metastases than in primary tumors. Our findings highlight LT{beta} as a bone niche-induced factor that promotes tumor cell seeding and dormancy reactivation, underscoring its potential as a therapeutic target for preventing bone metastatic relapse in patients with breast cancer.

cell biology↗

bioRxiv2023

Osteoclast-Cancer Cell Metabolic Symbiosis Renders PARP Inhibitor Therapy Resistance in Bone Metastasis

Seventy percent of patients with late-stage breast cancer develop distal bone metastases; however, the mechanism by which the metabolic microenvironment affects resistance to therapy remains unknown. We investigated the metabolic bone microenvironment and identified glutathione metabolism as the top pathway in osteoclasts, which provides feedback to tumor cells to help neutralize oxidative stress and generate PARP inhibitor (PARPi) therapy resistance. GPX4, the critical enzyme responsible for glutathione oxidation, was upregulated during PARPi therapy through stress-induced ATF4-dependent transcriptional programming. The increased absorption of glutamine and the upregulation of GPX4 expression work in concert to enhance glutathione metabolism in cancer cells. Human clinical sample analysis of paired primary breast tumor and bone metastasis samples revealed that GPX4 was significantly induced in bone metastases. Combination therapy utilizing PARPi and zoledronate, which blocks osteoclast activity and thereby reduces the microenvironmental glutamine supply, generates a synergistic effect in reducing bone metastasis. Thus, our results identified an essential metabolic symbiosis between bone-resident cells and metastatic cancer cells during PARPi therapy. SIGNIFICANCEOsteoclast-derived glutamine is taken up by tumor cells to synthesize glutathione and neutralize the ROS generated by PARPi. This is the first example of "metabolic symbiosis" in therapeutic resistance of bone metastasis.

cancer biology↗

bioRxiv2022

Molecular and morphological analyses of the genus Episoriculus with the description of a new subgenus

Shrews in the genus Episoriculus are among the least known mammals in China. It occurs mainly in the Himalayas and the Hengduan Mountains. We report the sequencing and analyses of one mitochondrial gene (Cyt b) and three nuclear genes (Apob, Brca1, and Rag2) for 77 specimens, and analyses of morphological measurements for 56 specimens. Phylogenetic and morphological studies answer three longstanding questions. First, Episoriculus sacratus and E. umbrinus are valid species, and not subspecies of E. caudatus. Second, Pseudosoriculus fumidus is a valid taxon that does not belong to the genus Episoriculus. Third, the genus Episoriculus has eight valid species: E. baileyi, E. caudatus, E. leucops, E. macrurus, E. sacratus, E. soluensis, Episoriculus sp., and E. umbrinus. Ultimately, we erected subgenus Longacauda subgen. nov. for morphologically distinct E. macrurus, which leaves the nominate subgenus Episoriculus with the remaining seven congeners.

synthetic biology↗

bioRxiv2022

Expansion and Adaptive Evolution of the mTERF Gene Family in Plants

Mitochondrial transcription termination factor (mTERF) genes are encoded in the nucleus and bind to nucleic acids to regulate the replication, transcription and translation of mitochondrial genomes. Plants possess a large family of mTERF genes that play important roles in regulating organellar gene expression and stress response. However, their origin and expansion in land plants has not been examined. Here, we conducted a comprehensive molecular evolution analysis of 611 mTERF genes identified in 18 plant species, including algae, moss, fern, gymnosperm and flowering plants. Higher plants have more mTERF genes compared to lower plants, forming a huge higher plant-specific clade (M-class mTERF genes). M-class mTERF genes occur in clusters, suggesting that tandem duplication contributed to their expansion. Compared to other mTERF genes, M-class mTERF genes have undergone rapid evolution, and several significant positively selected sites were located in nucleic acid-binding sites. The strong correlation between the number of M-class mTERF genes and corresponding mitochondrial genome variation suggests that the rapid evolution of M-class mTERF genes might account for the changes in the complex machinery for expression regulation of plant mitochondrial genomes, providing molecular evidence for the host-parasite interaction hypothesis between the nucleus and mitochondria.

plant biology↗

bioRxiv2020

Connexin 46 and connexin 50 gap junction channel open stability and unitary conductance are shaped by structural and dynamic features of their N-terminal domains

The connexins form intercellular communication channels, known as gap junctions (GJs), that facilitate diverse physiological roles in vertebrate species, ranging from electrical coupling and long-range chemical signaling, to coordinating development and nutrient exchange. GJs formed by different connexins are expressed throughout the body and harbor unique channel properties that have not been fully defined mechanistically. Recent structural studies have implicated the amino-terminal (NT) domain as contributing to isoform-specific functional differences that exist between the lens connexins, Cx50 and Cx46. To better understand the structural and functional differences in the two closely related, yet functionally distinct GJs, we constructed models corresponding to CryoEM-based structures of the wildtype Cx50 and Cx46 GJs, NT domain swapped chimeras (Cx46-50NT and Cx50-46NT), and point variants at the 9th residue (Cx46-R9N and Cx50-N9R) for comparative MD simulation and electrophysiology studies. All of these constructs formed functional GJ channels, except Cx46-50NT, which correlated with increased dynamical behavior (instability) of the NT domain observed by MD simulation. Single channel conductance (γj) also correlated well with free-energy landscapes predicted by MD, where γj of Cx46-R9N was increased from Cx46 and the γjs of Cx50-46NT and Cx50-N9R was decreased from Cx50, but to a surprisingly greater degree. Additionally, we observed significant effects on transjunctional voltage-dependent gating (Vj-gating) and open-state dwell times induced by the designed NT domain variants. Together, these studies indicate that the NT domains of Cx46 and Cx50 play an important role in defining channel properties related to open-state stability and single channel conductance.Competing Interest StatementThe authors have declared no competing interest.AbbreviationsGJgap junctionGjgap junctional coupling conductanceγjsingle gap junction channel conductanceIjmacroscopic transjunctional currentijsingle gap junction channel currentCx46sheep connexin 46Cx50sheep connexin 50Vjtransjunctional voltageMDmolecular dynamicsr.m.s.d.root mean square deviationr.m.s.f.root mean square fluctuationPMFpotential of mean forceView Full Text

biophysics↗