Search PubMedSearch

Biomedical subjects

Ling Zhou

Publications and source records attributed to Ling Zhou.

4 recordsLinked to original sources

A novel allele of Sh1 facilitates the development of waxy-sweet corn from waxy corn.

Waxy corn and sweet corn represent 2 major classes of fresh-eating corn, each with distinct sensory attributes and nutritional compositions. Developing a new variety that combines both waxy and sweet traits would address rising consumer demand and expand new market potential. From a fast neutron-mutagenized population of the waxy corn inbred line HB522, we isolated a novel mutant, designated as wx-sweet, whose kernels simultaneously exhibit waxy and sweet characteristics at the milk-filling stage. Through bulked segregant analysis combined with fine mapping, we mapped the causal locus to SHRUNKEN1 (Sh1) on chromosome 9, which was confirmed by an allelism test with a characterized Mu-insertion allele of Sh1. A 7,227-bp Copia-type long terminal repeat retrotransposon insertion was identified in exon 2 of Sh1 in the wx-sweet mutant by long-read sequencing. Consistently, the novel sh1 allele significantly reduced sucrose synthase activity. Genetic and physiological analyses demonstrate that sh1 and wx1 act synergistically to fine-tune carbohydrate metabolism in the endosperm. Integrated transcriptomic and metabolomic profiling uncover extensive transcriptional reprogramming and redirected metabolic flux, leading to substantial accumulation of sucrose and a range of oligosaccharides. These metabolic shifts underlie the unique simultaneous dual waxy-sweet texture in fresh-eating wx-sweet kernels. In summary, our work not only provides valuable genetic resources for breeding next-generation fresh-eating corn but also, for the first time, elucidates the molecular mechanism by which the sh1 and wx1 mutations cooperatively shape the waxy-sweet endosperm phenotype.

Zea mays

Structural and functional characterization of a conserved cryptic epitope on SARS-CoV-2 spike S2 subunit.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive evolution since its emergence in 2019, underscoring the continuous need for vaccines and therapeutics effective against multiple variants of concern (VOCs). The S2 subunit of the viral spike (S) glycoprotein is highly conserved among sarbecoviruses, making it an attractive target for broadly protective countermeasures. To elucidate the S2 antigenic landscape, we employed yeast surface display to isolate S2-targeted antibodies from COVID-19 convalescent donors. Biophysical characterization revealed that these S2 apex-directed antibodies preferentially bind to open spike conformations and a stabilized S2 construct but not to the closed, trimeric prefusion spike. Cryo-electron microscopy structures defined a cryptic epitope encompassing the upper helix and fusion peptide proximal region on S2. This epitope is conserved among sarbecoviruses but remains largely occluded in the closed prefusion conformation of the spikes. As a result, the antibodies exhibited weak neutralization activity against SARS-CoV-2 pseudoviruses, failed to neutralize authentic viruses, and did not provide protection in a lethal mouse challenge model using a mouse-adapted SARS-CoV-2 strain. These findings highlight a non-neutralizing epitope on S2 capable of eliciting antibodies during SARS-CoV-2 infection in humans and provide valuable reagents for probing S2 conformational dynamics and optimizing S2-based vaccine antigens.

Spike Glycoprotein, Coronavirus

Prospective clinical validation of targeted long-read sequencing for preimplantation genetic testing of α-thalassaemia.

BACKGROUND: Preimplantation genetic testing for monogenic disorders (PGT-M) can prevent transmission of severe α-thalassaemia, but conventional workflows remain limited by family-specific assay design for direct variant detection, dependence on additional family samples for haplotype construction, and labour-intensive multi-step procedures across several platforms. Targeted long-read sequencing-based PGT-M for α-thalassaemia (tlrPGT-α-thal) integrates direct variant detection and haplotype linkage analysis within a single assay, but prospective clinical validation is lacking. METHODS: This prospective clinical study enrolled 103 families at high risk of transmitting α-thalassaemia at a reproductive medicine centre between August 2024 and March 2025. All families underwent blinded parallel analysis using both conventional NGS-based PGT-M (comparator) and tlrPGT-α-thal. RESULTS: In the primary concordance analysis, tlrPGT-α-thal was fully concordant with conventional NGS-based PGT-M (507/507, 100.0%; exact 95% CI, 99.3-100.0). Direct variant detection was successful in 501/507 embryos (98.82%; 95% CI, 97.4-99.6), haplotype linkage was established in 505/507 embryos (99.61%; 95% CI, 98.6-100.0), and one meiotic recombination event was identified. Among 93 families proceeding to embryo transfer, 57 pregnancies underwent invasive prenatal diagnosis, and all were concordant with the corresponding tlrPGT-α-thal results. Of the 26 comparator-inconclusive embryos, tlrPGT-α-thal resolved 6 complex cases, including cases with incomplete pedigrees or insufficient informative SNPs. Among the remaining 20 embryos with HBA-region aneuploidies, genotype and parental origin could be determined in 12. CONCLUSIONS: The findings show that tlrPGT-α-thal enables direct detection of diverse α-thalassaemia-causing variants together with efficient haplotype linkage analysis within a single workflow, without requiring family-specific assay design or additional family samples. The method demonstrated high diagnostic accuracy while providing added value in complex scenarios. Taken together, tlrPGT-α-thal represents a simplified and broadly applicable strategy for α-thalassaemia PGT-M.

Humans

Genome-Wide In Vivo RNAi Screening Identifies HOXD4 as a Tumor Metastasis Suppressor in Colorectal Cancer.

Metastasis remains a major therapeutic challenge in colorectal cancer, highlighting an urgent need to elucidate its underlying molecular mechanisms. In this study, an in vivo screening system integrating genome-wide short hairpin RNA library and next-generation sequencing identifies six candidate metastasis suppressors, among which Homeobox D4 (HOXD4) shows the most pronounced effects. Clinicopathological analyses reveal significant HOXD4 downregulation in tumor tissues relative to adjacent normal tissues, with reduced expression strongly correlating with aggressive tumor features. Functional assays demonstrate that HOXD4 depletion enhances migration, invasion, and tumorsphere formation in HCT116 cells, while ectopic HOXD4 overexpression reverses these malignant phenotypes in SW620 cells. Mechanistically, HOXD4 suppresses epithelial-mesenchymal transition (EMT) by directly binding to the promoter of Forkhead box Q1 (FOXQ1), a key driver of EMT and stemness, and thereby transcriptionally repressing its expression. Immunohistochemistry confirms an inverse correlation between HOXD4 and FOXQ1 expression in clinical specimens. Rescue experiments substantiate that HOXD4 exerts its metastasis-suppressing functions via FOXQ1 regulation. Collectively, these findings not only establish an efficient platform for screening tumor metastasis suppressors, but also identify HOXD4 as a master transcriptional regulator of the FOXQ1-EMT axis, providing a promising target for metastasis interception.

Humans