Biomedical subjects

Chen Qian

Publications and source records attributed to Chen Qian.

4 recordsLinked to original sources

PubMed2026

Advancing proteomic discovery through optimized multi-stage scoring and deep learning-enhanced open search.

MOTIVATION: Protein search engines are essential for interpreting mass spectrometry data into biological insight. Current tools often face limitations in sensitivity when analyzing complex modern datasets, and lack a unified framework that effectively integrates deep learning features for both restricted and open searches, especially for scenarios aimed at discovering unknown modifications. RESULTS: We present pFind+, a high-performance search engine for data-dependent acquisition (DDA) proteomics, extending pFind. It introduces an enhanced raw scoring that delivers substantially improved pre-filtering ability, while recovering most of the computational overhead through a tailored acceleration strategy. Coupled with an enhanced rescoring framework that effectively integrates deep learning features, pFind+ uniquely supports high-sensitivity, DL-enhanced open search, enabling comprehensive PTM discovery while incorporating hardware-aware inference optimizations for practical deployment. Evaluations across diverse datasets demonstrate its superior sensitivity, with gains of 12.7%-29.3% (average 17.9%) in restricted search and 8.0%-38.4% (average 25.8%) in open search over the best existing tools.

Deep Learning↗

PubMed2024

A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer.

Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint and stimulatory genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the Cancer Genome Atlas Program (TCGA) dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.

Humans↗

PubMed2005

Role of N-methyl-D-aspartate receptor in hyperoxia-induced lung injury.

Glutamate (Glu) N-methyl-D-aspartate (NMDA) receptor is present in the lungs, and NMDA receptor antagonist MK-801 attenuates oxidant lung injury. We hypothesized that Glu excitotoxicity may participate in the pathogenesis of hyperoxia-induced lung injury. To determine possible pulmonary protective effects, we administered 0.05 ml/kg MK-801 or saline intraperitoneally daily to neonatal rats exposed to more than 95% oxygen in air. After 7 days, MK-801 decreased the hyperoxia-associated elevation of wet-to-dry lung weight, total leukocyte and neutrophil counts, total protein and lactate dehydroase in BAL fluid, total myeloperoxidase activity, and lung pathological injury. MK-801 inhibited hyperoxia-associated increments in reactive oxygen species production and NF-kappaB production. Hence, NMDA receptor antagonist MK-801 ameliorates hyperoxia-induced lung injury in neonatal rats, and is associated with decreased reactive oxygen species and NF-kappaB. We conclude that Glu may play an important role in hyperoxia-induced lung injury by activation of NMDA receptor.

Animals↗

PubMed2002

Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12.

OBJECTIVE: Injection of dendritic cells (DC) engineered with recombinant adenoviral vectors to produce interleukin-12 (IL-12) inside experimental murine tumors frequently achieves complete regressions. In such a system the function of CD8(+) T cells has been shown to be an absolute requirement, in contrast to observations made upon depletion of CD4(+) T cells, which minimally affected the outcome. The aim of this work was to study the possible involvement of natural killer (NK) cells in this setting. MATERIALS, METHODS, AND RESULTS: Depletions with anti-AsialoGM1 antiserum showed only a small decrease in the proportion of complete regressions obtained that correlated with induction of NK activities in lymphatic tissues into which DC migrate, whereas combined depletions of CD4(+) and NK cells completely eliminated the antitumor effects. Likewise in vivo neutralization of interferon-gamma (IFN-gamma) also eliminated those therapeutic effects. Trying to define the cellular role played by NK cells in vivo, it was observed that injection of cultured DC inside the spleen of T- and B-cell-deficient (Rag1(-/-)) mice induced upregulation of NK activity only if DC had been adenovirally engineered to produce IL-12. In addition, identically transfected fibroblasts also activated NK cells, indicating that IL-12 transfection was the unique requirement. Equivalent human DC only activated in vitro the cytolytic and cytokine-secreting functions of autologous NK cells if transfected to express human IL-12. CONCLUSIONS: Overall, these results point out an important role played by NK cell activation in the potent immunotherapeutic effects elicited by intratumoral injection of IL-12--secreting DC and that NK activation under these conditions is mainly, if not only, dependent on IL-12.

Animals↗