Search PubMed⌕ Search

Biomedical subjects

Wen Li

Publications and source records attributed to Wen Li.

7 recordsLinked to original sources
PubMed2026

Characteristics of an NDM-1-producing Klebsiella pneumoniae strain belonging to ST105.

Uncommon multilocus sequence types (MLSTs) of NDM-producing Klebsiella pneumoniae may pose a significant threat to patients, although they are often overlooked in surveillance studies. Characterizing these isolates is therefore important for infection control. In this study, the antimicrobial susceptibility and pathogenicity of K. pneumoniae strain KP_WXD, pertaining to the atypical sequence type ST105, were evaluated, including capsular polysaccharide (CPS) production, biofilm formation, and resistance to serum killing. Whole-genome sequencing (WGS) was performed to analyze its genomic features. K. pneumoniae KP_WXD strain was resistant to all tested β-lactam agents. Its virulence was lower than that of K. pneumoniae strains ST11-KL64 and NTUH-k2044 used as references, while its biofilm formation ability was stronger than that of both strains. WGS analysis revealed carriage of IncF and IncN plasmids carrying multiple antibiotic resistance genes, alongside blaNDM-1 and blaCTX-M, integrated into well-characterized mobile genetic elements. Moreover, both blaNDM-1 and blaCTX-M-harboring plasmids were transferable to E. coli J53 by conjugation without significant fitness cost on the recipient strain.

Klebsiella pneumoniae↗
PubMed2026

Multimodal features and prognostic risk assessment in locally advanced gastric cancer patients following neoadjuvant therapy based on machine learning algorithms: a multicenter study.

BACKGROUND: Neoadjuvant therapy (NAT) is recommended for locally advanced gastric cancer (LAGC), but some patients respond poorly. We aimed to construct a multimodal model integrating CT images, transcriptomic sequencing, and clinicopathological data to assess prognosis in LAGC patients receiving NAT. MATERIALS AND METHODS: This multicenter study included 505 LAGC patients who underwent NAT. Radiomic features were extracted from preoperative CT images of 505 patients. RNA-seq was performed on 277 post-NAT specimens, with additional data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases (n&#x2009;=&#x2009;804). Patients were divided into training (168 cases), internal validation (72 cases), and external validation cohorts. Machine learning algorithms identified key radiomic, molecular, and clinical features associated with NAT response, which were then integrated into a multimodal model to predict overall survival (OS) and disease-free survival (DFS). RESULTS: Six radiomic and three molecular features significantly associated with NAT response were selected. Radiomic risk (hazard ratio [HR]: 4.0, P&#x2009;<&#x2009;0.001) and molecular risk (HR: 7.1, P&#x2009;<&#x2009;0.001) were independent prognostic factors. By integrating radiomic risk, molecular risk, and clinical characteristics, a multimodal model (MuMo) was constructed.The C-index results (OS, C-index&#x2009;=&#x2009;0.855; DFS, C-index&#x2009;=&#x2009;0.786) demonstrated that MuMo outperformed the single-modality models and ypTNM staging.Mechanistic analysis suggested that the efficacy of neoadjuvant therapy was significantly enriched in immune-inflammatory pathways. CONCLUSIONS: MuMo can effectively predict postoperative survival risk in LAGC patients receiving NAT, serving as a powerful tool for optimizing prognostic assessment.

Humans↗
PubMed2026

A G-Quadruplex-Activated Near-Infrared Chemiluminescent Probe for In Situ Hepatic Imaging of the Hepatitis C Virus Genome.

Real-time monitoring of viral replication is essential for infectious disease diagnosis and antiviral drug development. The G-quadruplex (G4), a conserved regulatory element within viral genomes, represents a significant endogenous biomarker for tracking viral activity. However, imaging viral G4s in deep tissues remains a challenge for current optical technologies due to severe photon attenuation and autofluorescence. Herein, we report Lumin680, the first near-infrared (NIR) chemiluminescent probe directly activated by conserved viral G4 conformations. Its chemiluminescence was triggered by parallel G4, emitting in the NIR optical window (680&#xa0;nm) with a 104.6-fold signal enhancement. Notably, the luminescence of Lumin680 could penetrate up to 1.2&#xa0;cm of biological tissue, outperforming traditional G4 fluorescent probe. In vivo, Lumin680 enabled the rapid visualization of orthotopic hepatitis C virus (HCV) genome RNA-presenting mini-organ within 5 min post-intravenous administration. Furthermore, the chemiluminescent intensity of Lumin680 quantitatively mapped the therapeutic efficacy of clinical direct-acting antivirals (DAAs) at both the cellular and whole-animal levels, exhibiting high concordance with the gold-standard quantitative RT-PCR (qPCR). This study not only provides a powerful G4 specific chemiluminescent tool but also establishes a novel paradigm for the non-invasive, in situ diagnosis and precise therapeutic monitoring of viral infections.

G-Quadruplexes↗
PubMed2026

The investigation of human cerebrospinal fluid exosome in spinal cord injury.

Spinal cord injury (SCI) leads to severe neurological and functional impairments, yet reliable biomarkers for assessing injury severity and predicting recovery remain limited. Cerebrospinal fluid (CSF) is in direct contact with the central nervous system and provides a valuable source for detecting molecular changes after SCI. Although exosomal microRNAs (miRNAs) and proteins are increasingly recognized as mediators of intercellular communication, the role of human CSF exosomes in SCI has not been systematically investigated. To identify exosome-based biomarkers and potential therapeutic targets, we analyzed CSF and serum exosomes from patients with acute SCI using RNA sequencing and proteomic profiling. Weighted gene co-expression network analysis identified 6 gene modules significantly associated with injury severity and neurological recovery at 3 months. Proteomic analysis revealed a 5-protein panel that distinguished complete from incomplete SCI and a 4-protein panel that predicted neurological improvement. Additionally, 15 CSF-specific and 9 serum-specific exosomal miRNAs were identified independent of injury severity. Among 10 tested miRNAs associated with neurological recovery, 7 regulated astrocyte proliferation, and 6 promoted neurite extension and synapse formation. Overall, this study provides a comprehensive characterization of CSF exosomal miRNAs and proteins in human SCI and identifies molecular signatures associated with injury severity and recovery.

Humans↗
PubMed2026

Bioinformatic analysis reveals the potential association of ESRP1 with the splicing of cytoskeleton-associated genes in doxorubicin-resistant MCF7 breast cancer cells.

BACKGROUND: Breast cancer remains one of the most prevalent malignancies among women, with doxorubicin resistance posing a significant challenge that undermines treatment success and survival outcomes. Aberrant alternative splicing (AS), driven by dysregulation or mutations in splicing factors (SFs), is implicated in cancer initiation, progression, and drug resistance. This study aims to investigate the association of the epithelial cell-specific splicing factor ESRP1 with doxorubicin resistance in breast cancer, focusing on how ESRP1 deficiency correlates with AS changes that promote chemoresistance. METHODS: We analyzed RNA-sequencing (RNA-seq) data from doxorubicin-resistant (MCF7-DR) and parental (MCF7) breast cancer cell lines to identify enhanced alternative splicing events (ASEs) and changes in ESRP1 expression; we further leveraged The Cancer Genome Atlas (TCGA)-BRCA cohort to construct an SF-RASE correlation network for screening core SFs (including ESRP1). An integrative analysis combining crosslinking immunoprecipitation (CLIP-seq) data and The Cancer Genome Atlas (TCGA) database was performed to validate ESRP1 binding targets and assess the association between ESRP1-related splicing and cytoskeleton organization. RESULTS: We observed extensive AS changes and significantly downregulated ESRP1 expression in MCF7-DR cells. Integrative analysis identified 61 high-confidence ASEs that correlate with ESRP1 expression. Further bioinformatic integration suggests that ESRP1 expression is associated with the splicing patterns of SPTBN1, MAP2K7, FGFR3, and CYB561A3-four genes involved in cytoskeleton organization-though direct experimental verification to confirm a causal regulatory relationship between ESRP1 and the splicing of these genes is still pending. CONCLUSIONS: Our findings suggest that ESRP1 expression is closely associated with doxorubicin resistance in breast cancer cells, with concomitant alterations in key ASEs linked to cytoskeletal remodeling that correlate with ESRP1. Exploring the ESRP1-related splicing network may offer new strategies to overcome chemoresistance and improve patient outcomes. However, the small cell line sample size (n&#x2009;=&#x2009;2 per group) constrains the robustness of ASE and SF-ASE correlation findings, and these results should be interpreted with caution and require further validation with larger sample cohorts.

Alternative splicing↗
PubMed2026

Identification of cryosensitive niches and a targetable FOS/AP&#x2011;1 program in the human ovarian cortex by single&#x2011;cell and spatial transcriptomics.

BACKGROUND: The ovary is a vital and dynamic reproductive organ. Ovarian tissue cryopreservation (OTC) plays a vital role in preserving female fertility. However, the cellular subtypes most susceptible to cryoinjury and the molecular mechanisms underlying cryopreservation-associated damage remain poorly understood. This study aimed to identify cell populations vulnerable to freezing-thawing and to elucidate the key transcriptomic alterations and signaling pathways associated with ovarian cryoinjury at the single-cell and spatial levels. METHODS: Ovarian cortical tissues from patients undergoing three gender reassignment surgery (GRS) were divided into fresh and vitrification-rapid warming groups. Following collagenase IV digestion, 10x&#x2009;Genomics single-cell RNA-seq was used for dissociated ovarian cell suspensions (27,185 fresh and 25,480 frozen-thawed cells). Eight major cell clusters were identified. Additionally, 110 oocytes (66 fresh, 44 vitrification-rapid warming) were isolated and analyzed using the Smart-seq2 platform. Spatial transcriptomics was performed via BGI Stereo-seq. Molecular validation was performed via &#x3b2;-galactosidase staining, immunofluorescence, and qRT-PCR. RESULTS: Cryopreservation significantly altered the activity of pathways related to focal adhesion, oxidative stress, and apoptosis, particularly in stromal and perivascular cells. The number of FOS-positive perivascular cells was notably increased after vitrification-rapid warming, whereas the number of PTGDS-positive stromal cells decreased. Oocyte analysis revealed that cryopreservation primarily disrupted pathways involved in the cell cycle and meiosis, although the damage was not irreversible, supporting the relative safety of long-term cryostorage. Spatial transcriptomics and functional validation further confirmed the rapid and robust activation of the FOS/AP-1 pathway after vitrification-rapid warming, particularly in perivascular and granulosa cells. Treatment with T-5224 (a FOS/AP-1 inhibitor) significantly rescued the morphology and function of cultured frozen-thawed ovaries. CONCLUSIONS: Stromal and perivascular cells are the main cell types that are sensitive to ovarian cryopreservation. The FOS/AP-1 pathway is markedly activated after, suggesting the exacerbation of metabolic impairment. In oocytes within the ovarian cortex, the cell cycle and meiosis-related physiological processes were the primary processes affected.

Female↗
PubMed2025

MLL1 downregulation drives hair cell ferroptosis via mitochondrial and endoplasmic reticulum stress mechanisms through PERK-eIF2&#x3b1;-ATF4-Chop and PI3K/Akt-Lrp1 signaling pathway.

BACKGROUND: Sensorineural hearing loss is characterized by irreversible hair cell (HC) degeneration. Ferroptosis, which is marked by the accumulation of reactive oxygen species and elevated levels of lipid peroxidation products, has been shown to contribute to drug-mediated auditory impairment. This study aimed to elucidate the role of mixed-lineage leukemia 1 (MLL1) in HC survival in the auditory system. METHODS: The HEI-OC1 auditory cell line and postnatal cochlear explants were evaluated using MM-102, a specific MLL1 histone methyltransferase inhibitor. Western blotting, quantitative polymerase chain reaction, electron microscopy, and immunofluorescence were used to elucidate the role of MLL1 in regulating ferroptosis in HC injury. RNA sequencing (RNA-seq) was used to analyze the molecular mechanisms of MLL1 intervention in HC injury from an epigenetic perspective. RESULTS: Our findings demonstrated that immunofluorescence staining revealed a crucial role of MM-102 in promoting intracellular accumulation of lipid peroxides and ferrous ions. Subsequent analysis showed MLL1 downregulation-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, with transmission electron microscopy imaging confirming ultrastructural alterations in mitochondria and ER. Mechanistic investigations identified the PERK-eIF2&#x3b1;-ATF4-Chop signaling axis as the regulatory pathway, evidenced by Western blotting quantification of phosphorylated PERK (p-PERK), ATF4, and Chop levels. RNA-seq analysis revealed 741 differentially expressed genes (335 upregulated and 406 downregulated). Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis specifically highlighted significant enrichment of the PI3K/Akt-Lrp1 pathway, with corresponding activation patterns of phospho (p)-Akt and Lrp1 confirmed through Western blotting analysis. CONCLUSIONS: MLL1 downregulation initiates ferroptosis in cochlear HCs. This process is intrinsically associated with the activation of mitochondrial dysfunction and ER stress. The study highlights the importance of MLL1 in HC survival, suggesting its potential as a therapeutic target for treating hearing loss.

Endoplasmic Reticulum Stress↗