Biomedical subjects

Xiao Liu

Publications and source records attributed to Xiao Liu.

6 recordsLinked to original sources

PubMed2026

GA4+7 alleviates pear fruit semi-russeting partly by suppressing PRX-mediated lignin deposition.

Pear fruit semi-russeting is a surface disorder that frequently occurs during fruit development and significantly diminishes fruit appearance quality and commercial value. Although Gibberellin 4 + 7 (GA4+7) has been used to reduce fruit surface defects in horticultural crops, the physiological and molecular mechanisms underlying its inhibitory effect on pear fruit semi-russeting remain poorly understood. In this study, preharvest GA4+7 treatment of 'Cuiguan' pear significantly reduced russet coverage and lignin accumulation in mature fruit skin without adversely affecting fruit size, fruit shape index, or total soluble solids content. Integrated metabolomic and transcriptomic analyses revealed that GA4+7 treatment was associated with the repression of phenylpropanoid and lignin biosynthesis at both metabolic and transcriptional levels. Among the lignin-related differentially expressed genes, two class III peroxidase genes, PpyPRX22 and PpyPRX65, were strongly downregulated by both GA4+7 and bagging treatments. Both proteins localized to the cell wall, and transient expression assays in pear fruit skin supported positive roles for PpyPRX22 and PpyPRX65 in lignin deposition. Furthermore, dual-luciferase reporter assays combined with transient overexpression experiments suggested that several PpyMYB transcription factors may regulate PpyPRX expression and lignin accumulation, with PpyMYB138 and PpyMYB139 significantly activating PpyPRX22 and/or PpyPRX65 promoter activity. Taken together, these results suggest that GA4+7 alleviates pear fruit semi-russeting at least partly by reducing lignin deposition in the fruit skin, with PpyPRX22 and PpyPRX65 potentially contributing to this process.

Class III peroxidase↗

PubMed2026

Small GTPase RAN-driven PNET2 oligomerization and phase separation at the nuclear lamina promote nuclear envelope integrity in plants.

The nuclear envelope is a fundamental organizer of eukaryotic cells, yet how plants regulate its architecture and integrity remains poorly understood. In this study, we identified the plant inner nuclear membrane protein PLANT NUCLEAR ENVELOPE TRANSMEMBRANE 2 (PNET2) as a scaffold that maintains nuclear envelope integrity and genome stability. Loss of PNET2 function compromises nuclear membrane structure and sensitizes cells to DNA damage, whereas overexpression drives aberrant nuclear membrane expansion. Biochemically, PNET2 cooperates with the nuclear lamin protein KAKU4 and CROWDED NUCLEI 1 within the nuclear lamina to promote nuclear membrane remodeling, a process driven by biomolecular condensate formation via their intrinsically disordered regions. We further uncovered a direct interaction between PNET2 and the small GTPase RAN. Structural modeling and biochemical analyses revealed that its active GTP-bound form stimulates PNET2 oligomerization, potentially promoting its phase separation to drive membrane expansion. Genetic analyses showed that PNET2 and RAN function in a shared pathway essential for nuclear membrane integrity. Together, our findings define a regulatory module that orchestrates GTPase signaling to sustain nuclear membrane homeostasis in plants, positioning PNET2 as a nexus linking membrane dynamics, nuclear lamina organization, and genome protection.

PNET2↗

PubMed2026

Comparative evaluation of probe-capture and conventional metagenomic sequencing across multiple clinical sample types, with analysis of paired bronchoalveolar lavage fluid and blood samples.

Conventional metagenomic next-generation sequencing (mNGS) suffers from host nucleic acid interference and poor performance in low-biomass samples. Probe-capture metagenomic sequencing (PC-mNGS), which enriches microbial targets via hybridization probes, shows superior sensitivity but lacks systematic multi-sample evaluations. This study compared PC-mNGS and mNGS across diverse clinical specimens (bronchoalveolar lavage fluid [BALF], blood, cerebrospinal fluid [CSF]) and assessed the clinical utility of pathogen co-detection in paired BALF-blood samples from sepsis patients. A total of 282 samples (81 BALF, 141 blood, 25 CSF, 35 others) sequenced by both PC-mNGS and mNGS were analyzed. Additionally, 621 paired BALF-blood samples from sepsis patients with pulmonary infections were evaluated. PC-mNGS achieved higher pathogen detection rates (66.67% vs 57.10%, P = 0.000198) than mNGS, particularly in blood (66.67% vs 47.52%, P = 2.5 × 10⁻⁵). PC-mNGS detected more bacteria (19 species exclusive) and fungi (11 species exclusive) than mNGS. Viruses showed comparable detection. BALF and CSF exhibited high overall agreement (OPA: 96.30% and 88%, respectively), while blood had lower concordance (NPA: 54.05%, OPA: 70.92%). A total of 60.55% of BALF-positive samples (PC-mNGS) had co-detected pathogens in blood. Gram-negative bacteria (e.g., Klebsiella pneumoniae) and fungi (e.g., Candida albicans) showed higher blood co-detection rates than viruses. In this study, PC-mNGS detected more pathogens and showed a higher positivity rate than mNGS in blood samples. BALF sequencing data, particularly bacterial reads per million (RPM), may predict bloodstream co-detection, aiding in sepsis management. However, clinical validation and integration with traditional diagnostics are needed to confirm utility. This study highlights PC-mNGS as a promising tool for complex infections but underscores the need for rigorous multi-context validation.IMPORTANCEAccurate and rapid identification of pathogens is critical for effective treatment of severe infectious diseases, such as sepsis. This study demonstrates that probe-capture metagenomic sequencing (PC-mNGS) detected more pathogens in blood samples compared to conventional metagenomic sequencing, especially for bacterial and fungal infections. By analyzing paired lung and blood samples, we show that high pathogen levels in lung fluid may predict bloodstream infection, offering a potential early warning for clinicians. These findings support the use of PC-mNGS as a more sensitive diagnostic tool, which could lead to faster, more targeted therapies and better outcomes for patients with complex infections.

Humans↗

PubMed2026

CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.

Glioblastoma (GBM), the most aggressive central nervous system (CNS) malignancy, currently lacks curative therapeutic options. While immunotherapy has revolutionized treatment for many cancers, GBM remains refractory to immune-based interventions due to the absence of effective immunotherapeutic targets. Here, through CRISPR screening, we identify Niemann-Pick C1-like 1 (NPC1L1) as a previously unrecognized key driver of GBM progression. Mechanistically, NPC1L1 modulates cholesterol metabolism to concurrently enhance tumor cell stemness and suppress CD8+ T-cell activation, thus inducing tumor progression. Notably, combined treatment with ezetimibe (NPC1L1 inhibitor) and anti-PD-1 antibody elicited potent antitumor activity in GBM orthotopic mouse models. Collectively, these findings establish NPC1L1 as a critical regulator of GBM pathogenesis, underscoring the translational potential of targeting NPC1L1-mediated cholesterol metabolism for developing novel GBM immunotherapies.

Humans↗

PubMed2026

Discovery of the Underlying Mechanism of Ginger Juice Processed Ziziphi Spinosae Semen for Its Sedative-Hypnotic Effect on Insomnia Mice via Regulation of HPA Axis and cAMP/PKA Signaling Pathway.

Based on Traditional Chinese Medicine (TCM) theory, the efficacy and mechanism of Ginger juice processed Ziziphi Spinosae Semen (GJPZSS) for treating insomnia, particularly stress-related types, were investigated to provide empirical evidence. An insomnia model was induced in mice by DL-4-chlorophenylalanine (PCPA) and chronic tail clamping. The sedative effect was evaluated by behavioral tests. Serum components from GJPZSS were analyzed by UHPLC-Q-TOF-MS/MS, and 64 potential targets were identified. The cAMP signaling pathway was enriched as the core pathway by Kyoto Encyclopedia of genes and genomes (KEGG) analysis and was validated by molecular docking. GJPZSS was demonstrated to prolong sleep time, reduce immobility time, increase 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) levels, decrease hypothalamic-pituitary-adrenal (HPA) axis levels, and suppress neuronal death. The reduction of the cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the brain was also significantly inhibited. It was concluded that the sleep-improving effect of GJPZSS was mediated through the regulation of the HPA axis and the cAMP/PKA/CREB/BDNF signaling pathway.

Animals↗

PubMed2025

Screening of the key single nucleotide polymorphisms in type 2 diabetes mellitus complicated with lower extremity arterial disease by machine learning.

OBJECTIVES: Diabetic lower extremity arterial disease (LEAD) is a manifestation of diabetic lower extremity vascular complications. This study aimed to screen the key single nucleotide polymorphism (SNP) gene signature in patients with type 2 diabetes mellitus (T2DM) and LEAD. METHODS: A total of 147 patients with T2DM complicated by LEAD and 144 patients with T2DM without LEAD were enrolled for transcriptome sequencing. The Plink software was used to preprocess the data. Five machine learning methods were adopted to build the SNP diagnosis models. The receiver operating characteristic (ROC) curve was used to quantify the predicted probabilities of the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the cluster Profiler package. Finally, regression statistical analysis was used to correlate the key SNPs with clinical information and biochemical indicators. RESULTS: A total of 24 SNPs were retained and 10 SNPs were risk allele genes. Nine SNPs (rs7412, rs1800629, rs699947, rs3918242, rs668, rs1800470, rs1800449, rs1800469, and rs1024611) were identified as the key SNPs sites. GO and KEGG pathway analyses revealed that these genes are mainly enriched in fluid shear stress and atherosclerosis. Finally, rs1800449 was associated with low-density lipoprotein cholesterol (LDL-C). With high density lipoprotein cholesterol (HDL-C), related site was rs1024611. The sites associated with total cholesterol (CHOL) were rs1800449 and rs7412.The site associated with apolipoprotein B (APOB) and apolipoprotein A1 (APOA1) were rs1800470 and rs1800469. CONCLUSION: This study authenticated nine SNPs for the diagnosis of T2DM patients with LEAD, which will be of great significance in the development of diagnostic molecular biomarkers for T2DM patients.

Humans↗