Author

Zehong Lin

View on Semantic Scholar

2 papers indexed here

We haven’t gathered this author’s papers yet. Follow them and we’ll fetch their work.

Not the right person? Other researchers publish under this name.

Open access Aug 2026

Unraveling the pathogenic mechanisms of osteoarthritis and obesity: An integration of GWAS, cellular specificity, and spatial transcriptomics

Objective This study aims to systematically elucidate the shared and specific genetic basis of osteoarthritis (OA) and obesity by integrating large-scale genome-wide association study (GWAS) summary statistics, cross-tissue quantitative trait loci (QTLs), and single-cell and spatial transcriptomic data. Method The research employed a multi-omics integrative analysis pipeline. First, a meta-analysis was conducted on GWAS data for OA and obesity. Next, tissue- and spatial-specific enrichment analyses were performed using methods such as QTLEnrich, MAGMA, and gsMap. Key steps included the application of single-cell analysis, Cell-stratified mendelian randomization (csMR), and the ECLIPSER/CELLECT framework to identify specific cell types. Finally, hub genes were identified using hdWGCNA. Results The results revealed significant enrichment of genetic risk signals for OA and obesity in brain tissues, including the cortex and pituitary gland. At the cellular level, T cells were identified as the highest-priority shared cell type for both diseases. Hub genes—GSN, CALD1, EBF1, LHFPL6, and TIMP3—were identified through co-expression network analysis. Spatial transcriptomic analysis further mapped the genetic risk signals to brain regions during embryonic development. Conclusion This study precisely anchors the genetic risk of OA and obesity to specific brain regions, cell types, and developmental time windows, providing a novel perspective for understanding the pathological mechanisms of OA.

Zehong Lin, Jihu Wei, Honghai Zhou · Osteoarthritis and Cartilage... · 0 citations

Open access Aug 2026

A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand

ABSTRACT Targeted protein degradation represents a promising therapeutic strategy, yet its broader application is often limited by the scarcity of usable E3 ligases. Glutathione peroxidase 4 (GPX4) is a key target for inducing ferroptosis, but achieving sustained and potent inhibition remains challenging with conventional enzymatic inhibitors. Herein, we report the first small‐molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand. The azide‐based degrader DK‐5070 effectively drives potent GPX4 degradation, achieving a DC50 of 17.4 nM and a Dmax of 84%, thereby outperforming larger PROTAC‐based degraders. Notably, DK‑5070 exhibits potent antitumor activity both in vitro (IC50 = 47.21 nM) and in vivo (TGI = 41.8%), demonstrating significant efficacy as a GPX4 degrader. Mechanistic studies reveal that degradation is mediated through recruitment of the oncogenic E3 ligase UHRF1, which is frequently overexpressed in tumors, underscoring the potential for tumor‐specific protein degradation. This demonstrated small‐molecule degraders that recruit UHRF1 to facilitate targeted degradation of GPX4. In this system, the azide group functions as a minimal recruitment ligand, thereby expanding the E3 ligase toolbox and offering a promising strategy for targeted cancer therapy.

Zehong Lin, Kang Duan, Rui Wan et al. · Advancement of science · 0 citations