Biomedical subjects

Hanlin Liu

Publications and source records attributed to Hanlin Liu.

3 recordsLinked to original sources

PubMed2026

PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer is characterized by redox adaptation and metabolic plasticity, but the mechanisms linking these processes remain incompletely understood. Integrating bulk, single-cell, and spatial transcriptomic analyses, we identified PRDX1 as a malignant epithelial cell-associated factor linked to adverse outcome. Genetic gain- and loss-of-function studies showed that PRDX1 promoted proliferation, motility, and xenograft growth while limiting reactive oxygen species accumulation and mitochondrial apoptosis. Proteomic and biochemical analyses identified an association between PRDX1 and SCD1. PRDX1 prolonged the SCD1 protein half-life without detectably altering SCD1 transcript abundance and increased USP7-SCD1 co-precipitation. USP7 removed K48-linked polyubiquitin chains from SCD1 and prevented its proteasomal degradation, whereas catalytically inactive USP7 failed to deubiquitinate SCD1. Deletion of PRDX1 residues 157-199 weakened its association with SCD1 and reduced USP7-SCD1 co-precipitation. Depletion of SCD1 or USP7 suppressed PRDX1-dependent growth in vitro and in xenografts. These findings support a model in which PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer↗

PubMed2026

Calcium-Sensing Receptor Activation Disrupts Phosphatidylserine Asymmetry and Promotes Calcium Oxalate Crystal-Induced Epithelial Injury in Renal Tubular Epithelial Cells.

BACKGROUND: Calcium oxalate (CaOx) crystal retention on the renal tubular epithelium is a key step in urolithiasis. Phosphatidylserine (PS) exposure may facilitate crystal-cell adhesion, but the upstream signaling mechanisms and the relative contributions of impaired inward PS flipping versus outward PS redistribution remain unclear. MATERIALS AND METHODS: Global proteomic profiling using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (2-DE/MALDI-TOF/TOF) in an immortalized human proximal tubular epithelial cell line (HK-2) cells exposed to calcium oxalate monohydrate (COM) identified upregulation of the calcium-sensing receptor (CaSR). HK-2 cells were treated with COM with or without the CaSR antagonist NPS2390 or the CaSR agonist gadolinium chloride (GdCl3). Bidirectional PS transport was assessed using an N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) (NBD)-labeled phosphatidylserine (NBD-PS) fluorescence-quenching assay, and surface PS exposure was measured by annexin V binding. Aminophospholipid translocase (APLT) expression, APLT-dependent inward PS transport, crystal adhesion, oxidative stress, and apoptosis-related signaling were evaluated. RESULTS: COM increased CaSR expression, enhanced surface PS exposure, and promoted crystal adhesion with concurrent oxidative stress and apoptosis-related signaling. COM induced a CaSR-sensitive defect in APLT-dependent inward PS flipping: NPS2390 partially restored inward PS transport and APLT expression, whereas GdCl3 exacerbated these changes. In contrast, COM-enhanced outward PS redistribution and externalization was largely unaffected by CaSR modulation, indicating relative CaSR insensitivity of the outward process. Consistently, CaSR activation aggravated, while CaSR inhibition attenuated, crystal adhesion and injury-related readouts. CONCLUSIONS: COM was associated with enhanced crystal-cell adhesion, CaSR activation, and a CaSR-sensitive impairment of APLT-dependent inward PS flipping, whereas enhanced outward PS redistribution appeared largely CaSR-insensitive. Pharmacologic inhibition of CaSR attenuated epithelial injury and crystal retention-related readouts, suggesting that CaSR may represent a potential therapeutic target.

Receptors, Calcium-Sensing↗

PubMed2025

Genome-scale evolution and phylodynamics of swine influenza A viruses in China: a genomic epidemiology study.

BACKGROUND: Pigs are recognised as crucial intermediate hosts for the emergence of influenza viruses of pandemic potential. As the largest pork-producing nation, China hosts a complex ecosystem of swine influenza viruses (SIVs). We aimed to investigate the evolutionary processes, spatiotemporal dynamics, and biological characteristics of SIVs in China. METHODS: From Jan 15, 2016, to Dec 22, 2020, we collected nasal swabs from pigs at eight abattoirs and 16 swine farms in the Guangdong, Henan, and Shandong provinces of China, as part of SIV surveillance. SIVs were detected with RT-PCR. Positive samples underwent viral isolation and genome sequencing. We analysed evolution and spatiotemporal dynamics using the whole genomes of isolated SIVs, as well as genome sequences of SIV isolates from human infections worldwide retrieved from the Global Initiative on Sharing All Influenza Data and GenBank Flu databases up to April 28, 2024. Viral sequences without a sample collection area or date were excluded from the analysis. Viral receptor-binding properties and in-vitro replication of strains isolated in this study were evaluated with a solid-phase binding assay and various cell lines, including Madin-Darby canine kidney cells, porcine alveolar macrophages, primary porcine trachea epithelial cells, human bronchial epithelioid, and human lung adenocarcinoma epithelial (A549) cells. Viral replication and transmission studies were conducted in 33 guinea pigs and 13 pigs. Additionally, we collected serum samples from pig farm workers and members of the general public recruited by the Third Affiliated Hospital of Sun Yat-sen University between Feb 28 and May 11, 2023, to detect specific antibodies against Eurasian avian-like A(H1) and human-like A(H3N2) SIVs using the haemagglutination inhibition assay. FINDINGS: 23 (1·3%) of 1818 nasal swabs collected in abattoirs had SIVs; 22 (0·9%) of 2375 swabs from swine farms had SIVs. Further viral isolation yielded 39 strains of SIV. We identified 534 A(H1N1), 69 A(H1N2), and 92 A(H3N2) SIVs, representing 20 genotypes within the Eurasian avian-like lineage, 14 within the classical swine A(H1) lineage, and 16 within the human-like A(H3N2) lineage. The introduction of the A(H1N1)pdm/09 virus significantly influenced the internal gene pool of SIVs, enhancing genotypic diversity in China. Notably, the Eurasian avian-like A(H1), classical swine A(H1), and human-like A(H3N2) lineages showed human-mediated spread over long distances between provinces, with the Eurasian avian-like A(H1) lineage showing the most prevalent spread pathways. Eurasian avian-like A(H1) SIVs showed a preference for binding to sialic acid α-2,6 glycan receptors, predominantly found in humans, resulting in an increased production of progeny viruses in human airway epithelial cells, as well as effective transmission and infectivity among guinea pigs and pigs. Among 54 eligible serum samples collected from pig farm workers (24 from slaughterhouses and 30 from swine farms), 23 (43%) were seropositive for Eurasian avian-like A(H1) SIVs and 46 (85%) for human-like A(H3N2) SIVs. Among 100 eligible samples from members of the general public, 14 (14%) were seropositive for Eurasian avian-like A(H1) SIVs and 85 (85%) for human-like A(H3N2) SIVs. INTERPRETATION: This study elucidates the evolutionary processes and spatiotemporal patterns of SIVs, highlighting potential risks to public health. These findings are crucial for informing public health interventions that aim to prevent future SIV epidemics in China and other countries worldwide. FUNDING: Scientific Innovation Strategy-Construction of High-Level Academy of Agriculture Science-Distinguished Scholar (R2020PY-JC001).

Animals↗