Biomedical subjects

Yu Huang

Publications and source records attributed to Yu Huang.

12 recordsLinked to original sources

PubMed2026

A robust biotechnology induces artificial genomic duplication via transient RNAi-mediated suppression of OSD1 in rice.

Ploidy manipulation is a crucial strategy for generating germplasm in crop breeding. However, artificial genomic duplication, often induced by colchicine treatment, is associated with toxicity and unpredictability. Although mutations in OSD1 have shown promise for inducing genomic duplication, the instability of ploidy across generations limits their practical application. In this study, we developed a Plant Polyploidization via Gene Interference (PPGI) system that utilizes transient RNAi-mediated suppression of OSD1 to efficiently induce artificial genomic duplication, demonstrating obvious potential for producing autotetraploids. We first validated this system by successfully generating PPGI-induced autotetraploid plants from the Taichung65 cultivar. These PPGI-induced plants exhibited notable differences from Taichung65 but resembled the existing Taichung65-4x line obtained through colchicine treatment. Haplotype analysis indicated that the OSD1 RNAi fragment is conserved across 2,908 rice cultivars. Consequently, we employed the same PPGI vector to develop autotetraploid lines from various germplasms, including another japonica cultivar, seven indica cultivars, and one Oryza rufipogon line. The probability of genomic duplication achieved by our PPGI method was higher than that obtained by colchicine treatment. Typically, autotetraploid lines exhibit severe sterility in the first generation following polyploidization. Leveraging fertile neo-tetraploid rice and the PPGI system, we designed and verified two strategies to directly induce fertile autotetraploid germplasms in the first generation, thereby substantially shortening the breeding cycle. Our method provides a universal, efficient, and non-toxic approach for inducing autotetraploid rice germplasms and contributes to enriching fertile autotetraploid rice germplasm resources.

OSD1↗

PubMed2026

TFPI-high myofibroblast states and a meta-program-related five-gene prognostic signature in breast cancer.

Intratumoral heterogeneity and tumor-microenvironment interactions limit prognostic stratification in breast cancer, but the prognostic relevance and cellular context of recurrent transcriptional meta-programs remain unclear. We aimed to derive a meta-program-related prognostic signature and characterize its component transcripts at single-cell resolution. Six paired institutional tumors and adjacent non-tumor tissues served as a proof-of-concept comparison. Univariable Cox screening and least absolute shrinkage and selection operator Cox regression were used to derive a five-gene score from a prespecified meta-program-related candidate set in The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) training cohort; the score was tested internally and assessed in GSE20685 using fixed coefficients and cohort-specific median cutoffs. GSE161529 single-cell transcriptomic data were used to map signature transcripts across 136,526 quality-controlled cells, while donor-aware pseudobulk analysis compared upper- and lower-quartile TFPI expression states in annotated myofibroblasts. The score comprised TCN1, FOXJ1, PIGR, SLAIN1, and TFPI and was associated with overall survival in the training, testing, and external cohorts, with concordance indices of 0.782, 0.756, and 0.721, respectively. TFPI transcripts were detected across endothelial, fibroblast, and myofibroblast compartments. TFPI-high myofibroblasts showed transcriptional enrichment of extracellular matrix and collagen fibril organization, transforming growth factor beta signaling, epithelial-mesenchymal transition, and myogenesis, together with lower oxidative phosphorylation and fatty acid metabolism programs. In bulk TCGA-BRCA tissue, TFPI expression correlated positively with stromal (r = 0.48), immune (r = 0.25), and composite microenvironment scores (r = 0.40; all p < 0.001). These findings identify a hypothesis-generating five-gene bulk-tissue prognostic signature and an expression-associated TFPI-high myofibroblast state but do not establish a discrete lineage, the cellular source of bulk TFPI, a TFPI-dependent mechanism, or clinical utility. Independent prospective cohorts, spatial and protein-level validation, and functional perturbation studies are required.

Journal Article↗

PubMed2026

Decoding Primary Open-Angle Glaucoma: A Multi-Omics Approach to Identify Druggable Effector Genes.

PURPOSE: Genomewide association studies (GWAS) have identified numerous primary open angle glaucoma (POAG) risk loci, yet most reside in non-coding regions with unclear function. Mapping these loci to effector genes can elucidate disease mechanisms, identify functionally conserved variants, improve cross-ancestry risk prediction by reducing population-specific noise, and uncover shared therapeutic targets. METHODS: Here, we integrate European POAG GWAS with six types of multi-omics molecular Quantitative Trait Locis (xQTLs) using multi-trait colocalization to identify candidate effector variants and evaluate their cross-population relevance using genetic risk score (GRS) analysis, and their therapeutic potential through drug target prioritization. RESULTS: We identified 25 POAG effector variants colocalized with at least one xQTLs. In non-European populations, effector variants showed stronger effect size correlations with Europeans than non-colocalized variants (Pearson r2 = African 0.85 vs. 0.71; East Asian 0.81 vs. 0.69; and Latin American 0.91 vs. 0.75). Effector variants also had smaller allele frequency variations across populations (average interquartile range [IQR] = 0.15 vs. 0.20). The genetic risk score based on effector variants performed comparably to the genome-wide significant single-nucleotide polymorphism (SNP)-based GRS in non-European populations. Drug prioritization identified zinc, copper, sunitinib, probucol, and astemizole as potential common therapeutic agents for POAG and its subtypes. CONCLUSIONS: Our findings offer deeper insight into the molecular mechanisms underlying glaucoma and effector variants for developing more robust GRS models and broadly effective therapeutic strategies for POAG.

Humans↗

PubMed2026

The first near telomere-to-telomere genome assembly of Panulirus homarus homarus.

The scalloped spiny lobster (Panulirus homarus homarus) is an economically important decapod crustacean with high aquaculture potential. Several chromosome-level genomes of this species have been reported. But the lobster or even entire shrimps did not have the telomere-to-telomere assembly until now. Therefore, we present the first near telomere-to-telomere genome assembly of P. h. homarus generated by using pure Oxford Nanopore Technologies ultra-long (ONT) reads and Hi-C sequencing. The final assembly anchored to 73 chromosomes with a contig N50 of 41.1 Mb. 73 chromosomes contain entire 146 telomeres, of which 51 chromosomes have no gaps. A total of 38,396 protein-coding genes were predicted. BUSCO analysis showed a completeness score of 99.8%, indicating a high degree of assembly completeness. This high-quality genomic dataset provides a valuable resource for comparative genomics, evolutionary studies, and genome-assisted breeding of spiny lobsters.

Animals↗

PubMed2026

Nonuniform Association of Genetic Risk Scores for Intraocular Pressure.

IMPORTANCE: Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma, and genetic risk scores hold promise as a tool for screening for ocular hypertension. However, genetic risk scores for IOP have a nonuniform association across the range of IOP, which reduces their accuracy. OBJECTIVE: To test the hypothesis that nonuniform behavior of genetic risk scores for IOP is associated with a specific type of genetic interaction. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, post hoc genetic association studies were performed using linear and quantile regression in a sample of UK Biobank participants. Data were analyzed from January to September 2025. EXPOSURES: Ninety-eight genetic variants associated with IOP. MAIN OUTCOMES AND MEASURES: Tests were carried out for 98 genetic variants associated with IOP (P < 5.0 ×10-8) to examine (1) dominant or recessive genetic effects, (2) genotype × genotype interactions, (3) genotype × age interactions, and (4) genotype × sex interactions. RESULTS: A total of 98 235 participants (mean [SD] age, 58.1 [7.9] years; 52 168 female [53.1%]) were included in this analysis. More variants exhibited genotype × age interactions than expected by chance (14 of the 98 variants associated with IOP had at least nominal evidence of an interaction with age; P = 3.76 ×10-4). For 12 of these 14 variants, age increased rather than decreased the magnitude of the IOP vs genotype association. However, integrating age interactions into the genetic risk score construction process did not yield improved accuracy (incremental noninteraction model, R2 = 4.05; 95% CI, 3.82-4.31 and interaction model, R2 = 4.04; 95% CI, 3.80-4.27). There was little support for other types of genetic interaction. CONCLUSIONS AND RELEVANCE: In the current work, findings show minimal evidence that nonadditive allelic effects, genotype × genotype interactions, and genotype × sex interactions contributed to the nonuniform association of genetic variants with IOP across quantiles of IOP. Although a genetic risk score for IOP was more accurate in older vs younger individuals, efforts to account for genotype × age interactions in genetic risk score construction did not improve accuracy. These findings suggest other factors, such as gene-environment interactions, contribute to the nonuniform relationship of genetic variants with IOP.

Humans↗

PubMed2026

Leveraging environmental applications and risks of coal gangue: A critical review on authigenic inorganic heavy metals, organic contaminants, and the removal of exogenetic contaminants.

Coal gangue (CG) as bulk solid waste has seriously threatened the ecosystem. Therefore, identifying the key risk drivers and exploring feasible disposal methods for CG are essential for developing a sustainable strategy. However, there is currently a lack of comprehensive information that balances the contamination risks with the valuable constituents present in CG, which hinders its full potential for sustainable use without negative environmental impacts. Given the complex composition and associated risks, we propose that addressing the critical properties related to contamination is crucial for the efficient utilization of CG. On this premise, we summarized several practical resource pathways (ecological multifunctional materials, extraction of rare elements, and soil additives) that are more favorable for sustainable development relative to conventional disposals. Meanwhile, we also propose that coupling disposals could intensely reduce CG's environmental footprints and capital costs. Consequently, regardless of the number of challenges to be solved, we believe the CG has broad application prospects, and we hope this review will promote the conversion of CG into an asset with lower ecological and social impacts.

Metals, Heavy↗

PubMed2026

Author Correction: Endothelial IGFBP6 suppresses vascular inflammation and atherosclerosis.

Explore the source record for details and available documents.

Published Erratum↗

PubMed2026

Twenty-Three Years of Surveillance in Chinese Avian Pasteurella multocida Reveals Declining Antimicrobial Resistance but Increasing Therapeutic Challenges.

Pasteurella multocida (Pm) is an important veterinary and zoonotic pathogen that causes significant economic losses in poultry production. However, long-term surveillance studies integrating antimicrobial resistance (AMR), biocide tolerance, and genomic epidemiology of Pm remain scarce. In this study, we investigated the antimicrobial susceptibility, biocide tolerance, and the phenotypic associations of 136 avian Pm isolates collected from six provinces in China between 2002 and 2024. Whole-genome sequencing was performed to characterize population structure, identify antimicrobial resistance genes (ARGs), and assess genotype-phenotype concordance. The A:L1:ST129 lineage remained the predominant clone throughout the 23-year surveillance period, with a high prevalence of AMR-associated traits observed within this lineage. Although resistance to several commonly used antimicrobial classes declined significantly after 2021, florfenicol resistance continued to increase, suggesting an emerging challenge for the clinical management of pasteurellosis. While the isolates generally exhibited low tolerance to the four representative biocides tested, phenotypic correlations were observed between AMR profiles and biocide tolerance patterns. Furthermore, substantial phenotype-genotype discordance was observed, indicating that the presence of ARGs alone may not be sufficient to accurately predict antimicrobial susceptibility. Overall, this study provides a longitudinal assessment of long-term AMR trends, biocide tolerance, and genomic epidemiology of avian Pm in China, offering epidemiological evidence for monitoring AMR trends and improving antimicrobial management strategies in poultry production.

Animals↗

PubMed2025

STING inhibits LINE-1 retrotransposition through sorting ORF1p to lysosomes for degradation.

The cyclic dinucleotide sensor stimulator of interferon (IFN) genes (STING) is known for its critical role in interferon and inflammatory responses. In addition, STING also has functions independent of interferon induction. In this study, we report that STING restricts the mobilization of the cellular retrotransposon long interspersed nuclear element 1 (LINE-1) independent of cGAS and interferon induction. LINE-1 is the only active autonomous retrotransposable element in the human genome and its transposition can cause genetic and autoimmune diseases. STING inhibition of LINE-1 requires its dimerization. Mechanistically, STING interacts with LINE-1 ORF1p, then the complex translocates to the ER-Golgi intermediate compartment (ERGIC) and the Golgi followed by sorting to Rab7-positive lysosomes for degradation. Our data unveil a function of STING in maintaining host genome integrity by restricting LINE-1 retrotransposition via an IFN-independent mechanism.

Humans↗

PubMed2025

Fingolimod as a potent anti-Staphylococcus aureus: pH-dependent cell envelope damage and eradication of biofilms/persisters.

BACKGROUND: The urgent need for new antibacterial drugs has driven interest in repurposing therapies to combat Gram-positive biofilms and persisters. Fingolimod, an Food and Drug Administration (FDA)-approved drug for multiple sclerosis, shows bactericidal activity, particularly against Methicillin-resistant Staphylococcus aureus (MRSA) and biofilm-related infections. With a well-documented safety profile and strong translational potential, it aligns with World Health Organization's goals for antimicrobial repurposing. However, the action mode and mechanism of Fingolimod against gram-positive bacteria remain elusive. METHODS: This study utilized clinical Staphylococcus aureus (S. aureus), Enterococcus faecalis (E. faecalis), Streptococcus agalactiae (S. agalactiae). And their susceptibility to Fingolimod and other antibiotics was tested via Minimum Inhibitory Concentration (MIC) assays. Biofilm inhibition and hemolytic activity were evaluated using crystal violet staining, Confocal Laser Scanning Microscopy (CLSM), and hemolysis assays, respectively, while the effect of phospholipids on Fingolimod efficacy was assessed with checkerboard assays. Membrane permeability and integrity were measured using SYTOX green staining and transmission electron microscopy. Whole-genome sequencing was performed on Fingolimod-resistant S. aureus isolates to identify Single Nucleotide Polymorphisms (SNPs) linked to resistance. RESULTS: Our data indicated that Fingolimod exerted bactericidal activity against a wide spectrum of gram-positive bacteria, including S. aureus, E. faecalis, S. agalactiae. Moreover, Fingolimod could significantly eliminate the persisters, inhibit biofilm formation and eradicate in-vitro mature biofilms of S. aureus. The mechanism by which Fingolimod rapidly eradicated S. aureus involved a pH-dependent disruption of bacterial cell permeability and envelope integrity. Concomitantly, exogenous supplementation of phospholipids in the culture medium resulted in a dose-dependent increase in the MIC of Fingolimod. Specifically, the addition of 64 μg/mL of cardiolipin (CL) and phosphatidylethanolamine (PE) completely nullified the bactericidal activity of Fingolimod at a concentration of 4 times the MIC. After four months of Fingolimod exposure, the MIC values of S. aureus showed a slight increase, indicating that it is not prone to developing drug resistance. CONCLUSION: Fingolimod exhibits bactericidal activity against diverse gram-positive bacteria, with remarkable effects on S. aureus (including MRSA), disrupting bacterial cell structural integrity in a pH-dependent way and eradicating biofilms and persisters of S. aureus.

Biofilms↗

PubMed2024

Genetic analysis of partial duplication of the long arm of chromosome 16.

BACKGROUND: Pure partial trisomy 16q12.1q22.1 is a rare chromosome copy number variant (CNV). The primary clinical phenotypes associated with this syndrome include abnormal facial morphology, global developmental delay (GDD), short stature, and reported predisposing factors for atypical behavior, autism, the development of learning disabilities, and neuropsychiatric disorders. The dosage-sensitive genes associated with partial trisomy are not disclosed preventing to establish a genotype-phenotype correlation. METHODS: We report a case of a Chinese patient diagnosed with GDD and an abnormal facial shape, who was found to have partial trisomy 16 through karyotyping and high-throughput sequencing analysis. Karyotype and CNV tracing analyses were also conducted on the biological parents of the patient to assess for any chromosomal structural abnormalities. Additionally, we included 29 patients with pure partial trisomy 16q, reported in the DECIPHER database and the literature. We and performed a genotype-phenotype correlation analysis. RESULTS: The proband, a 2-year-old female, was found to have a de novo 21.96 Mb duplication located between 16q12.1q22.1, with no other deletions observed on other chromosomes, indicating a pure partial trisomy of 16q. Through genotype and phenotype analysis of 29 individuals, we found that patients with the duplicated region located at the distal region of 16q may exhibit more severe symptoms than those with duplication at the proximal region; however, no relationship was identified between phenotype and the size of the duplicated segment. CONCLUSION: We report, for the first time, a patient with partial trisomy 16q validated by multiple genetic tests, including CNV-seq, whole exome sequencing (WES), and karyotyping. It is speculated that partial trisomy of 16q may be associated with continuous gene duplication. However, functional studies are necessary to identify the causative gene or critical region linked to duplication syndrome of chromosome 16q.

Child, Preschool↗

PubMed2024

Genotype-phenotype spectrum and correlation of PHARC Syndrome due to pathogenic ABHD12 variants.

BACKGROUND: A comprehensive understanding of the genetic basis of rare diseases and their regulatory mechanisms is essential for human molecular genetics. However, the genetic mutant spectrum of pathogenic genes within the Chinese population remains underrepresented. Here, we reported previously unreported functional ABHD12 variants in two Chinese families and explored the correlation between genetic polymorphisms and phenotypes linked to PHARC syndrome. METHODS: Participants with biallelic pathogenic ABHD12 variants were recruited from the Chinese Deafness Genetics Cohort. These participants underwent whole-genome sequencing. Subsequently, a comprehensive literature review was conducted. RESULTS: Two Han Chinese families were identified, one with a compound heterozygous variant and the other with a novel homozygous variant in ABHD12. Among 65 PHARC patients, including 62 from the literature and 3 from this study, approximately 90% (57 out of 63) exhibited hearing loss, 82% (50 out of 61) had cataracts, 82% (46 out of 56) presented with retinitis pigmentosa, 79% (42 out of 53) experienced polyneuropathy, and 63% (36 out of 57) displayed ataxia. Seventeen different patterns were observed in the five main phenotypes of PHARC syndrome. A total of 33 pathogenic variants were identified in the ABHD12. Compared with other genotypes, individuals with biallelic truncating variants showed a higher incidence of polyneuropathy (p = 0.006), but no statistically significant differences were observed in the incidence of hearing loss, ataxia, retinitis pigmentosa and cataracts. CONCLUSIONS: The diagnosis of PHARC syndrome is challenging because of its genetic heterogeneity. Therefore, exploring novel variants and establishing genotype-phenotype correlations can significantly enhance gene diagnosis and genetic counseling for this complex disease.

Humans↗