Biomedical subjects

Lin Zhao

Publications and source records attributed to Lin Zhao.

4 recordsLinked to original sources

PubMed2026

Phosphoproteomic Analysis of GAP50-Deficient Parasites Reveals the Inner Membrane Complex Is Involved in Ion Regulation in Toxoplasma gondii.

The Alveolata group of organisms is characterized by a vesicular structure located beneath the plasma membrane. In apicomplexa, this structure is known as the inner membrane complex (IMC). The IMC acts as a scaffold during the budding of the daughter parasite and is utilized as a rigid base for the glideosome. In this study, we discovered that the phosphatase activity of GAP50 is crucial for its function in the biogenesis of the IMC. Through further phosphoproteomic analysis of parasites lacking GAP50, we identified that an NIPA family transporter is localized in the IMC. Knocking out TgNIPA1 significantly impairs the robust growth of the parasites. Additionally, expressing TgNIPA1 in a Salmonella strain lacking magnesium transporters could rescue the growth phenotype of bacteria under low magnesium conditions, indicating that it functions as an active magnesium transporter. Our results strongly suggest that the flattened vesicles of the IMC may play important roles in ion regulation in T. gondii.

Toxoplasma↗

PubMed2025

Endogenous fine-mapping and prioritization of functional regulatory elements in complex genetic loci.

Most genetic loci linked to polygenic traits are in non-coding regions, with complex regulation and linkage disequilibrium (LD), complicating causal variant and gene prioritization. We used multiplexed single-cell CRISPR interference and activation perturbations to investigate cis-regulatory element (CRE) and gene expression relationships within tight LD in the endogenous chromatin context. We demonstrated the prevalence of multiple causality in perfect LD (pLD) for independent expression quantitative trait loci (eQTLs) and uncovered fine-grained genetic effects on gene expression within pLD, which are difficult to decipher using traditional eQTL fine-mapping or existing computational methods. We found that over one-third of the causal CREs lack classical epigenetic markers prior to perturbation, and we functionally validated one of these hidden regulatory mechanisms. Leveraging Multiome single-cell epigenetic and sequence perturbations, we highlighted the regulatory plasticity of the human genome. Our study will guide the exploration of missing causal mechanisms underlying molecular trait regulation and disease development.

Humans↗

PubMed2025

Metagenome-Based Characterization of the Gut Virome Signatures in Patients With Gout.

The gut microbiome has been implicated in the development of autoimmune diseases, including gout. However, the role of the gut virome in gout pathogenesis remains underexplored. We employed a reference-dependent virome approach to analyze fecal metagenomic data from 102 gout patients (77 in the discovery cohort and 25 in the validation cohort) and 86 healthy controls (HCs) (63 and 23 in each cohort). A subset of gout patients in the discovery cohort provided longitudinal samples at Weeks 2, 4, and 24. Our analysis revealed significant alterations in the gut virome of gout patients, including reduced viral richness and shifts in viral family composition. Notably, Siphoviridae, Myoviridae, and Podoviridae were depleted, while Quimbyviridae, Retroviridae, and Schitoviridae were enriched in gout patients. We identified 359 viral operational taxonomic units (vOTUs) associated with gout. Enriched vOTUs in gout patients predominantly consisted of Fusobacteriaceae, Bacteroidaceae, and Selenomonadaceae phages, while control-enriched vOTUs included Ruminococcaceae, Oscillospiraceae, and Enterobacteriaceae phages. Longitudinal analysis revealed that a substantial proportion of these virome signatures remained stable over 6 months. Functional profiling highlighted the enrichment of viral auxiliary metabolic genes, suggesting potential metabolic interactions between viruses and host bacteria. Notably, gut virome signatures effectively discriminated gout patients from HCs, with high classification performance in the validation cohort. This study provides the first comprehensive characterization of the gut virome in gout, revealing its potential role in disease pathogenesis and highlighting virome-based signatures as promising biomarkers for gout diagnosis and future therapeutic strategies.

Humans↗

PubMed2024

A series of patients infected with the emerging tick-borne Yezo virus in China: an active surveillance and genomic analysis.

BACKGROUND: Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV. METHODS: In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses. FINDINGS: A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations. INTERPRETATION: Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms. FUNDING: National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Humans↗