Biomedical subjects

Yuan Liu

Publications and source records attributed to Yuan Liu.

9 recordsLinked to original sources

PubMed2026

Imaging‑based models for predicting cerebrovascular complications of carotid stenosis.

This is a protocol for a Cochrane review (prognosis). The objectives are as follows: Primary objective To systematically review and critically appraise multivariable prognostic models developed for adults (≥ 18 years) with carotid stenosis in which imaging biomarkers (e.g. plaque characteristics derived from magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) constitute the core predictors. The primary focus is to evaluate the predictive performance of these models for cerebrovascular complications - specifically ipsilateral ischaemic stroke and transient ischaemic attack (TIA) - which are the clinical outcomes to be predicted. Where feasible, we will summarise and compare the models' discrimination (C‑statistic/area under the curve (AUC)) and calibration (calibration‑in‑the‑large, calibration slope, observed‑to‑expected ratio) across studies, and assess their potential for clinical application and external validation. For the purpose of defining symptomatic carotid stenosis as an eligibility criterion and subgroup variable, we will include studies that also considered retinal ischaemia (e.g. retinal embolism, amaurosis fugax) as a qualifying event. Secondary objectives To describe the combinations of imaging markers, modelling techniques, sample sizes, and variable‑selection strategies used in the development of the included models To evaluate the performance of these models for additional secondary clinical outcomes: plaque progression or regression, incident high‑risk imaging features, and the transition from asymptomatic to symptomatic disease To explore whether predictive performance differs according to imaging modality (MRI versus CT versus contrast‑enhanced ultrasound (CEUS)) or technical protocol (e.g. 3 T versus 1.5 T, spectral CT versus conventional CT) For studies that report both cerebrovascular and broader cardiovascular outcomes (major adverse cardiovascular events, myocardial infarction, etc.), we will only extract the performance metrics relating to cerebrovascular events for the primary analysis. Performance metrics for cardiovascular outcomes will be considered exploratory and will not form part of the main synthesis.

Humans↗

PubMed2026

Genomics and social practices at Mogou and other Gansu sites during prehistoric trans-Eurasian exchange.

Beginning approximately 4,000 years ago, southwest-Asian-originating domesticated crops and livestock began appearing in Gansu, a key crossroads in northwestern China, yet the population dynamics and social practices underlying these historically transformative events in the region have not been fully explored. Despite the adoption of western domesticates, genome sequences of 149 individuals from the large Mogou cemetery and ten other sites in Gansu, dating between 4,700 and 3,000 years ago, revealed migrations within East Asian regions but no detectable evidence of genetic influence from western or central Eurasia, suggesting that early agricultural dispersals may have followed a model distinct from that documented in Europe and Central Asia. The Mogou cemetery represents a continuous community that interacted with surrounding regions but does not exhibit clear matrilocal or patrilocal residential patterns. We found no strong evidence that co-buried individuals represented biological relatives. Non-local ancestry appears to be linked to lower-status burial practices.

Humans↗

PubMed2026

An Aspergillus luchuensis isolated from a patient with hemoptysis insights from a comprehensive genome-based analysis: Case report.

RATIONALE: Asp luchuensis, a member of the A niger group, is widely used in food fermentation and rarely causes invasive pulmonary aspergillosis (IPA) in humans. Clinical cases of IPA induced by this strain are extremely scarce, and its genomic characteristics, virulence profiles, and pathogenic mechanisms remain poorly understood, resulting in insufficient clinical recognition of its invasive infection potential. PATIENT CONCERNS: A 57-year-old immunocompetent non-neutropenic male patient with a long-term smoking and drinking history presented with unexplained severe cough and massive hemoptysis (approximately100 mL) without other typical infectious symptoms. DIAGNOSES: Combined with chest computed tomography (CT) inflammatory lesions, positive galactomannan test, fungal PCR and metagenomic next-generation sequencing results, the patient was definitively diagnosed with probable A luchuensis-induced IPA. Genomic and transcriptomic analyses confirmed the pathogen as a variant A luchuensis strain with 3 key hypervirulence genes, highly active mitochondrial energy metabolism, and no specific antifungal resistance genes. INTERVENTIONS: The patient received standardized intravenous antifungal combination therapy with voriconazole and amphotericin B after confirmed diagnosis. OUTCOMES: The patient's cough and hemoptysis were significantly relieved after 10 days of treatment, with stable vital signs and no adverse drug reactions or disease progression. LESSONS: A luchuensis possesses strong invasive pathogenicity and can trigger IPA even in non-neutropenic immunocompetent individuals. Negative conventional microbial tests cannot exclude its infection, and mNGS is a reliable diagnostic tool. This strain is susceptible to routine antifungal drugs, and clinicians should raise awareness of atypical Asp species-induced invasive pulmonary infections.

Humans↗

PubMed2026

Identification of a novel and a recurrent CDC45 variant in a Chinese family with Meier-Gorlin syndrome 7 and a literature review.

INTRODUCTION: Meier-Gorlin syndrome 7 (MGORS7) is a rare autosomal recessive disorder characterized by primordial dwarfism, craniosynostosis, and patellar aplasia, caused by pathogenic variants of CDC45. Here, we report a Chinese patient presenting with classic hallmarks of MGORS7 alongside atypical clinical features, including hearing and visual impairments. METHODS: Clinical and radiological data were collected. Whole-genome sequencing and Sanger sequencing were performed to identify and validate the causative variants. Their functional effects were investigated using an exon-trapping assay, and a literature review of previously reported MGORS7 cases was conducted. RESULTS: Genetic analysis identified two compound heterozygous CDC45 variants: c.1416C>T (p.H472=) and c.1559+2T>A, which are a recurrent variant in the East Asian population and a novel variant, respectively. Our exon-trapping assay indicated that c.1559+2T>A induced aberrant splicing, generating transcripts predicted to undergo nonsense-mediated mRNA decay. Additionally, growth hormone therapy was initiated in our patient, with a noted improvement in growth parameters in the initial assessment and without immediate complications. The literature review identified a total of 32 CDC45 variants in 29 patients with MGORS7, who showed high heterogeneity in clinical phenotypes. DISCUSSION: Our study further expanded the mutational spectrum of CDC45 and provided a preliminary clinical observation suggesting that growth hormone therapy may be beneficial for growth retardation in patients with MGORS7.

CDC45↗

PubMed2025

A genome-wide CRISPRi screen identifies homologous recombination pathway as potential target for broad-spectrum antibiotic adjuvants.

INTRODUCTION: The widespread misuse and overuse of antibiotics have driven the emergence of multidrug-resistant and pan drug-resistant bacteria, constituting a formidable global health threat. Antibiotic adjuvants that potentiate the efficacy of existing antibiotics represent a particularly promising avenue to address this challenge. METHODS: We performed a genome-wide CRISPR interference (CRISPRi) screening to identify potential targets for broad-spectrum antibiotic adjuvants, which highlighted the homologous recombination pathway as a promising candidate. To functionally validate this pathway, we employed three strategies to suppress the expression and function of recA, a key component of homologous recombination, including a CRISPRi system delivered via transconjugation, a RecX-derived peptide (RecX-20) fused to a cell-penetrating motif, and a small-molecule inhibitor cisplatin validated by surface plasmon resonance. RESULTS: Disruption of the homologous recombination pathway not only significantly increased bacterial susceptibility to multiple classes of antibiotics, including quinolones, β-lactams, aminoglycosides, and nitrofurantoin, but also reduced horizontal gene transfer of antibiotic resistance. In addition, recA deficiency resulted in a cascade of physiological disruptions, including membrane damage, efflux pump dysfunction, oxidative stress imbalance and metabolic disruption. All three recA-targeting strategies enhanced the antibacterial activity, with cisplatin exhibiting the most pronounced potentiating effect both in vitro and in vivo. CONCLUSIONS: This study reveals that the homologous recombination pathway, particularly RecA, is a viable target for the development of broad-spectrum antibiotic adjuvant. Our findings provide mechanistic insights and practical strategies to restore the effectiveness of existing antibiotics and address the growing threat of antimicrobial resistance.

Anti-Bacterial Agents↗

PubMed2025

Suppression of LKB1-mutant lung adenocarcinoma by natural killer cells from females.

BACKGROUND: This study addressed the enigma of sex differences in smoking-related lung cancer, particularly focusing on the low LKB1 mutation frequency in female patients with lung adenocarcinoma. METHODS: Sex bias was studied with a genetically engineered mouse model and various tail-vein injection models. Immune cells were analyzed by antibody-depletion study, flow cytometry, and immunofluorescence. The relevance of our findings to human disease was validated by evaluating various lung adenocarcinoma datasets. All statistical tests are 2-sided. RESULTS: A statistically significant percentage of females are resistant to LKB1-mutant tumor formation in our models, reflecting this sex difference in humans. Natural killer (NK) cells were identified as a critical factor in this sex-biased response. This sex difference was observed primarily in LKB1-mutant lung adenocarcinoma, probably due to their low major histocompatibility complex class I level, making them the ideal target for NK cells through the missing-self recognition. Although females resistant to LKB1-mutant lung adenocarcinoma formation did not have enhancement of any specific NK subpopulation, our immunofluorescence analysis revealed high numbers of NKs in female lungs even with the presence of LKB1-mutant lung adenocarcinoma. Our gene set enrichment analysis of The Cancer Genome Atlas-lung adenocarcinoma dataset also showed that female LKB1-mutant lung adenocarcinoma patients have a stronger NK-mediated response after adjusting for other male-female differences using the LKB1 wild-type lung adenocarcinoma dataset. CONCLUSION: Females have a stronger NK-mediated response against LKB1-mutant lung adenocarcinoma, which was present in our mouse model and the human lung adenocarcinoma dataset. This study revealed a novel role of NK cells in suppressing LKB1-mutant lung adenocarcinoma in females, which should be assessed in the clinical setting in the future.

Killer Cells, Natural↗

PubMed2025

Boosting Quantification of N-Glycans by an Enhanced Isobaric Multiplex Reagents for Carbonyl-Containing Compound (SUGAR) Tagging Strategy.

Glycans are complex molecules composed of various monosaccharides and exhibit diverse, branched polymer structures. Extensive research has been conducted on mass spectrometry (MS)-based qualitative and quantitative glycan analysis due to their critical biological functions. However, traditional data-dependent acquisition (DDA) in MS analysis primarily selects a limited subset of abundant ions during MS1 scans for fragmentation in subsequent MS2 stages. In this study, we introduce an advanced isobaric labeling strategy that incorporates a large amount of content-relevant sample labeled with one isobaric tag channel as an additional boosting channel. This innovation enhances the efficiency of isobaric multiplex reagents for carbonyl-containing compound (SUGAR) tagging in quantitative glycomics. Notably, this approach significantly improves the characterization of low-abundance N-glycans and enables the detection of subtle quantitative differences in N-glycan profiling.

Polysaccharides↗

PubMed2025

RENBP inhibition amplifies metabolic glycan labeling efficiency of antigen-presenting cells in vitro and in vivo.

Metabolic glycoengineering of unnatural sugars provides a powerful tool to introduce unique chemical tags onto cell membrane for subsequent conjugation of cargos. However, the metabolic glycan labeling efficiency of antigen-presenting cells (APCs), the key mediators of adaptive immunity, is often low. Here, we report that APCs upregulate GlcNAc 2-epimerase (RENBP) and that RENBP inhibition leads to improved labeling efficiency of tetraacetyl-N-azidoacetylmannosamine (AAM) in APCs, including dendritic cells (1.2-fold), macrophages (1.3-fold), and B cells (1.4-fold) in vitro. RENBP inhibition can preferentially enhance AAM labeling efficiency in APCs than in non-APCs and selectively enhance the labeling efficiency of AAM over azido-galactosamine. We further demonstrate that RENBP inhibitors can improve AAM-mediated labeling of B cells and other APCs in vivo, with the largest enhancement for B cells (>3-fold) for 7 days. Our study uncovers a facile approach to improving metabolic glycan labeling of APCs, enabling the development of APC-targeted immunotherapies.

Animals↗

PubMed2021

A full-proteome, interaction-specific characterization of mutational hotspots across human cancers.

Rapid accumulation of cancer genomic data has led to the identification of an increasing number of mutational hotspots with uncharacterized significance. Here we present a biologically informed computational framework that characterizes the functional relevance of all 1107 published mutational hotspots identified in approximately 25,000 tumor samples across 41 cancer types in the context of a human 3D interactome network, in which the interface of each interaction is mapped at residue resolution. Hotspots reside in network hub proteins and are enriched on protein interaction interfaces, suggesting that alteration of specific protein-protein interactions is critical for the oncogenicity of many hotspot mutations. Our framework enables, for the first time, systematic identification of specific protein interactions affected by hotspot mutations at the full proteome scale. Furthermore, by constructing a hotspot-affected network that connects all hotspot-affected interactions throughout the whole-human interactome, we uncover genome-wide relationships among hotspots and implicate novel cancer proteins that do not harbor hotspot mutations themselves. Moreover, applying our network-based framework to specific cancer types identifies clinically significant hotspots that can be used for prognosis and therapy targets. Overall, we show that our framework bridges the gap between the statistical significance of mutational hotspots and their biological and clinical significance in human cancers.

Genomics↗