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Yue Liu

Publications and source records attributed to Yue Liu.

14 recordsLinked to original sources
PubMed2026

ADCY2 promoter hypomethylation in adolescents with borderline personality disorder: An RRBS study with targeted BSP replication.

BACKGROUND: Borderline Personality Disorder (BPD) is characterized by emotional dysregulation, impulsivity, and interpersonal instability. Although genetic and environmental contributions to BPD have been investigated, epigenetic correlates in adolescents remain poorly understood. The cyclic adenosine monophosphate (cAMP) signaling pathway is implicated in stress responsivity and emotion regulation, but its epigenetic variation in adolescent BPD remains understudied. METHODS: DNA methylation profiling was performed using Reduced Representation Bisulfite Sequencing (RRBS) in buccal epithelial DNA from adolescents with BPD (n = 15) and healthy controls (HC; n = 15). Differentially methylated regions (DMRs) were identified using metilene, a computational tool for detecting DMRs from bisulfite sequencing data, and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Associations between methylation signals and borderline personality features were examined. Adenylate cyclase 2 (ADCY2) promoter methylation was examined using targeted bisulfite sequencing PCR (BSP) in an independent cohort (BPD n = 5; HC n = 5). RESULTS: RRBS identified 7641 DMRs between BPD and HC, with enrichment in pathways related to neuronal signaling and synaptic organization. A hypomethylated DMR was detected in the ADCY2 promoter, a gene implicated in cAMP signaling. Lower ADCY2 promoter methylation was associated with greater clinical severity, including emotional dysregulation, borderline traits, anxiety symptoms, and self-injury behaviors (r=-0.71 to -0.83; all p < 0.0001). Hypomethylation of the ADCY2 promoter was replicated in the independent cohort. CONCLUSIONS: This exploratory two-stage epigenetic study suggests that ADCY2 promoter hypomethylation in peripheral buccal epithelial DNA is associated with core symptom dimensions of adolescent BPD. These findings support a role for cAMP-related epigenetic variation in BPD and warrant replication in longitudinal studies.

ADCY2↗
PubMed2026

Genomic epidemiology of clinically critical antibiotic resistance in Salmonella enterica causing bloodstream infections across six Chinese provinces, 1994-2023.

Clinically critical antibiotic-resistant Salmonella enterica (S. enterica) causing bloodstream infections remains a public health challenge. Here, we aim to reveal the emergence and trends of clinically important antibiotic resistance in S. enterica causing bloodstream infections using 833 isolates from six Chinese provincial-level administrative areas during 1994-2023. We identified 48 serovars and 64 sequence types (STs). Overall, 8.52% of 833 isolates were resistant or had decreased susceptibility to ciprofloxacin, 4.32% and 6.84% reported resistance or decreased susceptibility to third- and fourth-generation cephalosporins (3GCs and 4GCs), 1.80% reported resistance to fosfomycin, and 2.16% reported resistance to azithromycin. Across these six regions, azithromycin and fosfomycin resistance is increasing, as is decreased susceptibility or resistance to ciprofloxacin, 3GCs, and 4GCs, especially among younger children and elderly people. Clinically prioritized antibiotic resistance also varies by region, serovar, and age group. S. Paratyphi A genotype 2.3.3 strains are mainly divided into 2 lineages distributed in Guangxi and Shanghai. Within the scope of this passive surveillance dataset, S. Typhi genotype 4.3.1.2.1 was identified as the earliest documented case among the collected isolates. Our retrospective and longitudinal genomic epidemiology study provides critical data for the formulation of treatment guidelines and policies for bloodstream infections and for the monitoring and control of antimicrobial resistance.

Humans↗
PubMed2026

INPP5K-related muscular dystrophy caused by a novel synonymous splicing variant in a Chinese patient: a case report.

Congenital muscular dystrophies (CMDs) are a genetically heterogeneous group of disorders. Variants in the INPP5K gene, which encodes a phosphoinositide phosphatase, are a rare cause of CMD. The condition is commonly associated with muscle weakness, early-onset cataracts, and intellectual disability, and prior reports have primarily identified missense, frameshift, or deletion variants. We describe the first Chinese case of INPP5K-related muscular dystrophy in a 28-year-old male with a mild phenotype, notably lacking intellectual disability. His presentation included bilateral cataracts at age 5 and adolescent onset limb girdle weakness. Muscle magnetic resonance imaging (MRI) revealed a characteristic pattern of selective fatty infiltration, with severe involvement of gluteal and thigh muscles and striking sparing of the rectus femoris, sartorius, and gracilis. Genetic analysis identified compound heterozygous novel INPP5K variants: a missense c.274C>T, p.(Arg92Cys) and a synonymous c.261G>A, p.(Lys87=) change. Functional studies confirmed the synonymous variant causes aberrant splicing (exon 3 skipping), leading to a frameshift and premature termination p.(Leu52SerfsTer49). According to American College of Medical Genetics and Genomics guidelines, the c.274C>T and c.261G>A variants were classified as likely pathogenic and pathogenic, respectively. This first report of a Chinese patient with INPP5K-related muscular dystrophy broadens both the genetic and clinical spectrum of the disorder. We identify the first disease-causing synonymous variant (via aberrant splicing) and a novel hypomorphic missense variant p.(Arg92Cys), the combination of which explains the attenuated phenotype lacking intellectual disability. Our case highlights the critical role of RNA analysis in diagnosing non-canonical variants and confirms the universal diagnostic relevance of the characteristic muscle MRI pattern.

Adult↗
PubMed2026

Adipocyte-derived CRAMP-neutrophil serine protease interaction axis regulates innate cutaneous defense against Staphylococcus aureus.

Dermal adipocytes have emerged as active participants in cutaneous host defense. In parallel, adipocyte hypertrophy and hyperplasia-driven obesity has become a global public health priority and is strongly associated with increased risk and severity of bacterial infections. Here, we established and optimized two complementary S. aureus infection models-epidermal and subcutaneous-and in combination with diet-induced (HFD) and genetic (ob/ob) obesity, to systematically evaluate cathelin-related antimicrobial peptide (CRAMP) expression in adipocytes and its crosstalk with neutrophils. Obese mice displayed impaired cutaneous defense despite marked thickening of the fat layer, characterized by attenuated induction of adipocyte CRAMP and reduced local antibacterial activity. In vitro, CRAMP followed a biphasic pattern during adipocyte differentiation-upregulated at early stages but diminished with advanced maturation and lipid accumulation. Mechanistically, neutrophils processed adipocyte-derived CRAMP via serine proteases to generate shorter peptides with enhanced antibacterial activity. Collectively, these findings identify a CRAMP-neutrophil (serine protease) interaction axis as a key amplifier of cutaneous innate immunity and provide mechanistic insight into obesity-associated susceptibility to skin infection, suggesting potential avenues for targeted intervention.

Animals↗
PubMed2026

Neurodegeneration risk variants promote lysosomal TMEM106B fibril accumulation.

Variants in TMEM106B and GRN, which encode lysosomal proteins, interact through unknown mechanisms to increase the risk of age-related cognitive decline and neurodegeneration. Here, we show that these variants converge on a single molecular intermediate: the cleaved intra-lysosomal fibril core of TMEM106B, a precursor to amyloid fibrils that accumulate in the aging brain. A protein-coding TMEM106B risk variant (p.T185) drives fibril core accumulation by impairing its degradation and GRN risk variants amplify this effect. Mice over-expressing the fibril core develop hallmarks of neurodegeneration, and cryo-electron tomography reveals intra-lysosomal fibrils in cultured neurons, mice, and diseased human brain. In GRN-mutation carriers, in whom fibril burden is greatest, fibrils extrude through ruptured lysosomal membranes. These findings identify intra-lysosomal TMEM106B fibrillization as a convergent neurodegeneration mechanism and potential therapeutic target.

Journal Article↗
PubMed2026

Long-Term Warming Reduces Bacterial Diversity and Functional Potential in Temperate Forest Soil.

Soil microbes are key regulators of forest carbon cycling, yet how their diversity and functional potential respond to long-term warming remains poorly understood. Here, we report a five-year in&#xa0;situ warming experiment in a temperate forest, combining ten repeated measurements of microbial diversity and functional gene potential, as well as continuous monitoring of soil CO2 flux. We found that warming progressively reduced bacterial diversity and induced phylogenetically conserved community reorganization. Under warming, community composition shifted in a phylogenetically conserved manner. Warming generally reduced the abundance of microbial functional genes across most carbon-, nitrogen-, and phosphorus-cycling gene categories, except for genes associated with starch decomposition. Warming also altered the factors associated with soil CO2 flux: microbial diversity showed a stronger association with soil CO2 flux under long-term warming, whereas soil moisture was the dominant predictor in the control treatment. This warming-enhanced biodiversity control over soil CO2 flux was associated with shifts in microbial functional potential, particularly increases in starch-degrading genes and microbial biomass production potential. Together, our results suggest that warming can restructure microbial communities in ways that strengthen biodiversity-dependent regulation of soil carbon cycling, with implications for climate-carbon feedbacks.

Soil Microbiology↗
PubMed2025

CCDC137 knockdown suppresses bladder cancer progression by downregulating SCD.

BACKGROUND: The Coiled-coil domain-containing (CCDC) family, due to its unique protein structural domain and broad involvement in diverse biological processes, has emerged as a focus in oncology research. Nevertheless, its clinical significance and function in bladder cancer (BLCA) remain poorly defined. METHODS: Machine learning algorithms were employed to identify pivotal CCDC genes in the cancer genome atlas (TCGA), and a prognostic model was subsequently constructed. Multi-omics data encompassing pan-cancer cohorts, single-cell sequencing, and spatial transcriptomics were integrated to characterize the expression patterns and prognostic significance of Coiled-coil domain-containing 137 (CCDC137), a previously uncharacterized CCDC family member in BLCA. Tissue microarray confirmed CCDC137 abnormal expression in bladder carcinoma specimens. The effect of CCDC137 knockdown on BLCA progression was evaluated through CCK8 assay, clonogenic formation, wound healing, Transwell, and subcutaneous xenograft models. RNA sequencing, quantitative RT-PCR, and western blot were utilized to delineate its regulatory network. RESULTS: A prognostic model incorporating 10 CCDC genes was successfully established in the TCGA-BLCA cohort. Then, we found that CCDC137 exhibited pan-cancer overexpression and usually correlation with poor clinical outcomes. Immunohistochemistry further substantiated its dysregulation in bladder carcinoma. Integrated multi-omics analyses suggested associations between CCDC137 expression and a tumor immunosuppressive microenvironment. CCDC137 knockdown significantly suppressed bladder cancer cell proliferation and migratory capacity in vitro. Correspondingly, subcutaneous xenograft tumor growth was inhibited in vivo. Moreover, decreased expression of stearoyl-CoA desaturase (SCD), a key lipid metabolic enzyme, accompanied CCDC137 depletion. These findings collectively suggest a cancer-promoting role for CCDC137 in bladder carcinoma. CONCLUSIONS: This systematic investigation combining multi-omics bioinformatics analyses and experimental validation demonstrates the role of CCDC137 in bladder carcinoma progression, providing novel mechanistic insights into the pathogenesis of BLCA and offering a theoretical foundation for therapeutic targeting of CCDC137 in urothelial malignancies.

Urinary Bladder Neoplasms↗
PubMed2025

CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.

We profiled 2,961 cerebrospinal fluid (CSF) proteins in 1,005 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 1,066 proteins not measured in prior studies, using mass spectrometry (MS). We mapped protein quantitative trait loci (pQTLs) in CSF, compared them with brain and plasma pQTLs, and integrated them with Alzheimer's disease (AD) genome-wide association study (GWAS) data. We identified 1,417 index cis pQTLs for 654 unique genes and 130 index trans pQTLs for 94 unique genes. Cross-tissue and cross-proteomic-platform comparisons show broad consistency between MS-based CSF pQTLs and MS-based brain pQTLs as well as affinity-based CSF and plasma pQTLs. Lastly, through integrating CSF pQTLs with the largest AD GWAS, we identified 24 candidate AD causal proteins in CSF, including 10 novel and 14 previously identified in either brain, CSF, or plasma using similar approaches. These CSF AD candidate causal proteins are involved in immune response - notably humoral immunity (3 of 24) - that expands the role of the immune system in AD beyond innate immunity, as well as lysosomal function and neurovascular growth and remodeling. Together, our findings provide novel insights into AD biology and new targets for biomarker and therapeutic development.

Journal Article↗
PubMed2025

TCF25 serves as a nutrient sensor to orchestrate metabolic adaptation and cell death by enhancing lysosomal acidification under glucose starvation.

Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation. We focus on one candidate gene, Transcriptional Factor 25 (TCF25). We find TCF25 enhances lysosomal acidification by targeting V-ATPase, promoting autophagy and ATP generation under glucose starvation. However, prolonged glucose starvation constitutively activates ferritinophagy via TCF25, increasing lysosomal membrane permeability (LMP) and leading to lysosome-dependent cell death (LDCD). Knocking out TCF25 or V-ATPase components prevents cell death. Furthermore, TCF25 deficiency protects mice from hepatic ischemia-reperfusion injury. Our findings identify TCF25 as a crucial nutrient sensor that regulates lysosomal activity, offering potential therapeutic targets for metabolic and ischemic disorders.

Lysosomes↗
PubMed2025

Genomes of 211 Actinomycete Strains from Diverse Environments.

Actinomycetes are a highly diverse group of microorganisms that have long been recognized as a valuable source of antibiotics and other bioactive metabolites. Recent advances in genome mining have revealed a wealth of previously unexplored silent secondary metabolite biosynthetic gene clusters (smBGCs) in actinomycete genomes, underscoring their untapped bioactivity potential. Here, we present the genome sequences of 211 actinomycete strains isolated from various environmental sources, generated through high-throughput sequencing. The resulting genome assemblies exhibit high completeness and accuracy, offering high-quality data for downstream analyses and biological resource exploration.

Actinobacteria↗
PubMed2025

Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.

T-cell immunotherapy has progressed rapidly, evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer. This review explores engineering strategies, ranging from natural TCRs to synthetic receptors, that increase T-cell activation and therapeutic potential. We begin by highlighting the foundational role of native receptors in the T-cell response, emphasizing how these structural and functional insights inform the design of next-generation synthetic receptors. Comparisons between CAR and TCR-like synthetic receptors underscore their respective advantages in specificity, efficacy, and safety, as well as potential areas for further improvement. In addition, gene editing technologies such as CRISPR-Cas9 enable precise modifications to the T-cell genome, enhancing receptor performance and minimizing immunogenic risks. In addition to tumors, these engineered T cells can be directed against viral infections, autoimmune disorders, and other diseases. We also explore advanced strategies that engage multiple immune cell types to achieve synergistic, durable responses. By demonstrating how native and synthetic receptors collectively drive innovation, this review aims to inspire new research directions and ultimately expand the scope of T-cell engineering for universal therapeutic applications.

Humans↗
PubMed2025

Generative AI Models in Time-Varying Biomedical Data: Scoping Review.

BACKGROUND: Trajectory modeling is a long-standing challenge in the application of computational methods to health care. In the age of big data, traditional statistical and machine learning methods do not achieve satisfactory results as they often fail to capture the complex underlying distributions of multimodal health data and long-term dependencies throughout medical histories. Recent advances in generative artificial intelligence (AI) have provided powerful tools to represent complex distributions and patterns with minimal underlying assumptions, with major impact in fields such as finance and environmental sciences, prompting researchers to apply these methods for disease modeling in health care. OBJECTIVE: While AI methods have proven powerful, their application in clinical practice remains limited due to their highly complex nature. The proliferation of AI algorithms also poses a significant challenge for nondevelopers to track and incorporate these advances into clinical research and application. In this paper, we introduce basic concepts in generative AI and discuss current algorithms and how they can be applied to health care for practitioners with little background in computer science. METHODS: We surveyed peer-reviewed papers on generative AI models with specific applications to time-series health data. Our search included single- and multimodal generative AI models that operated over structured and unstructured data, physiological waveforms, medical imaging, and multi-omics data. We introduce current generative AI methods, review their applications, and discuss their limitations and future directions in each data modality. RESULTS: We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines and reviewed 155 articles on generative AI applications to time-series health care data across modalities. Furthermore, we offer a systematic framework for clinicians to easily identify suitable AI methods for their data and task at hand. CONCLUSIONS: We reviewed and critiqued existing applications of generative AI to time-series health data with the aim of bridging the gap between computational methods and clinical application. We also identified the shortcomings of existing approaches and highlighted recent advances in generative AI that represent promising directions for health care modeling.

Artificial Intelligence↗
PubMed2024

Molecular Analysis of Persistent and Recurrent Barrett's Esophagus in the Setting of Endoscopic Therapy.

INTRODUCTION: Early neoplastic progression of Barrett's esophagus (BE) is often treated with endoscopic therapy. Although effective, some patients are refractory to therapy or recur after apparent eradication of the BE. The goal of this study was to determine whether genomic alterations within the treated BE may be associated with persistent or recurrent disease. METHODS: We performed DNA sequencing on pre-treatment esophageal samples from 45 patients who were successfully treated by endoscopic therapy and did not recur as well as pre-treatment and post-treatment samples from 40 patients who had persistent neoplasia and 21 patients who had recurrent neoplasia. The genomic alterations were compared between groups. RESULTS: The genomic landscape was similar between all groups. Patients with persistent disease were more likely to have pre-treatment alterations involving the receptor tyrosine kinase pathway ( P = 0.01), amplifications of oncogenes ( P = 0.01), and deletions of tumor suppressor genes ( P = 0.02). These associations were no longer significant after adjusting for patient age and BE length. More than half of patients with persistent (52.5%) or recurrent (57.2%) disease showed pre-treatment and post-treatment samples that shared at least 50% of their driver mutations. DISCUSSION: Pre-treatment samples were genomically similar between those who responded to endoscopic therapy and those who had persistent or recurrent disease, suggesting there is not a strong genomic component to treatment response. Although it was expected to find shared driver mutations in pre-treatment and post-treatment samples in patients with persistent disease, the finding that an equal number of patients with recurrent disease also showed this relation suggests that many recurrences represent undetected minimal residual disease.

Humans↗