Biomedical subjects

Yu Tian

Publications and source records attributed to Yu Tian.

10 recordsLinked to original sources

PubMed2026

Natural variation in GmSOP5 regulates seed oil and protein content during soybean domestication.

Seed oil content, protein content, and yield are agronomically important, correlated traits that determine the economic value of soybean (Glycine max). However, improving seed quality and yield simultaneously is challenging because gains in one breeding target often compromise the other, and the genetic basis of this trade-off is poorly understood. Here, we performed a genome-wide association study of 429 diverse soybean accessions and identified Seed Oil and Protein 5 (SOP5), which encodes a kinesin protein, as a key locus associated with seed oil and protein content. Knockout and overexpression experiments demonstrated that GmSOP5 positively affects seed oil content and 100-seed weight and negatively influences seed protein content. GmSOP5 is located in a selective sweep region, and the domestication-related GmSOP5H1 allele is nearly fixed in cultivated soybean, contributing to increased seed size, weight, and oil content and reduced protein content. Field trials demonstrated that neither loss-of-function GmSOP5-edited mutants, which have increased seed protein content, nor GmSOP5-overexpression lines, which have increased seed oil content, differed significantly in yield from wild-type plants, because changes in plant architecture were offset by changes in seed weight. Our results shed light on soybean domestication and suggest how pleiotropy can be harnessed in breeding to enhance seed quality without compromising yield.

GWAS↗

PubMed2026

By comparing the effects of Lactobacillus paracasei KL1 and BK56 strains on yogurt quality, the optimal consumption time for 2 compound fermented yogurts was determined.

This study investigated the effects of 2 Lactobacillus paracasei strains, KL1 and BK56, on the physicochemical properties, microstructure, texture characteristics, and sensory quality of a compound fermented yogurt system (GK107: L. paracasei KL1, Leuconostoc mesenteroides G12S, Chr. Hansen Commercial Starter Culture; G56107: L. paracasei BK56, L. mesenteroides G12S, Chr. Hansen Commercial Starter Culture), and further integrated genomic and metabolomic analyses to infer their shelf-life and optimal consumption period. The results showed that GK107 yogurt maintained stable quality throughout the 28-d storage period (at d 28: pH 4.07; titratable acidity 93.25 °T; exopolysaccharide content 0.31 g/L; water-holding capacity 53.05%; sensory score 83), and rapidly formed a stable gel structure that persisted for an extended duration. In contrast, the quality of G56107 yogurt deteriorated during the later stage of storage (at d 28: pH 4.0; titratable acidity 98.4 °T; exopolysaccharide content 0.31 g/L; water-holding capacity 51.3%; sensory score 67). Genomic analysis revealed that, compared with the L. paracasei KL1 strain, the L. paracasei BK56 strain carried loss-of-function mutations in multiple key genes associated with flavor synthesis, polysaccharide metabolism, and proteolysis, including alsS, prtP, glpO, AWC33_RS01450, AWC33_RS00855, AWC33_RS01070, and AWC33_RS01805. These mutations may have played a role in the gradual flavor deterioration, and weak post-acidification control observed in G56107 yogurt during prolonged storage. Based on the above results, it is reasonable to suggest that GK107 yogurt is suitable for long-term storage with an optimal consumption period of 14 to 28 d, whereas G56107 yogurt is more suitable for short-term storage and recommended for consumption within the first 14 d.

Genomics↗

PubMed2026

Bacteroides cellulosilyticus-derived 2-hydroxyphenylacetic acid rectifies hepatic lipid homeostasis in MASLD by targeting the PPARγ-CD36 axis.

The gut microbiota plays an important role in the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD), but the specific molecular mechanisms involved have not been fully elucidated. In this study, human cohort studies were performed to identify that the relative abundance of Bacteroides cellulosilyticus (B. cellulosilyticus) was significantly decreased in patients with MASLD. Through the integration of metagenomic and metabolomic analyses, it was confirmed that B. cellulosilyticus and its metabolite 2-hydroxyphenylacetic acid (2HPAA) are key factors regulating the occurrence and development of MASLD. Single-cell sequencing and lipidomic analyses revealed that 2HPAA can enter the liver through the enterohepatic circulation to exert regulatory effects. Specifically, 2HPAA inhibits the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, thereby suppressing the expression of the fatty acid transporter CD36. Meanwhile, 2HPAA regulates lipid metabolism in hepatocytes by significantly enhancing palmitate conversion efficiency and inhibiting CD36 palmitoylation. This dual regulatory effect on CD36 expression and palmitoylation can reduce lipid accumulation in hepatocytes and ultimately alleviate MASLD progression. These findings reveal the mechanism by which B. cellulosilyticus and 2HPAA alleviate MASLD by targeting the PPARγ-CD36 pathway. This work provides a new perspective for the study of gut microbiota-host interactions in regulating liver diseases.

PPAR gamma↗

PubMed2026

Genome-wide association and selective sweep analyses reveal genetic loci for teat number trait in pigs.

Teat number is a key reproductive trait for the commercial pig industry, as an optimum number enhances weaned piglet survival rate. This study aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with teat number in the Large White sow. A total of 1000 French Large White sows were used in an analysis of total, left/right, and maximum unilateral teat number. Environmental factor, Spearman correlation, genome-wide association study (GWAS), linkage disequilibrium, and selective sweep analyses were conducted, with validation performed in a population of 1145 Landrace pigs. Genetic statistics showed that this population's teat number had moderate-low genomic heritability (h2 = 0.17-0.21) and weak negative correlation with weaned piglet litter weight. Parity and season affected teat development. GWAS identified 17 candidate SNPs on SSC 4, 7, and 17. Combined with selective sweep analysis, two key regions on SSC 7 were found, with four teat number-related SNPs, annotated to VRTN, DIO2, NRXN3. These candidate genes are associated with thoracic vertebrae development, hormone regulation during the early stage of teat formation, and nervous system development. These five SNPs showed similar results in the Landrace pig validation population; non-mutant homozygotes had 0.25-1.15 more teats than mutant ones in both populations. This study contributes to the identification of key variant loci associated with teat number-related traits in sows, thereby providing reliable molecular markers and a theoretical basis for marker-assisted selection of sow reproductive performance.

Animals↗

PubMed2026

Genome-wide CRISPR screen reveals PEX11B as a host restriction factor against ORFV through membrane fluidity regulation.

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

Animals↗

PubMed2025

Multi-Omics and Integrative Analytics in Natural Products Discovery.

Natural products (NPs) have long been an essential source of new bioactive compounds for drug discovery; however, traditional methods for screening and isolating these compounds can be slow and often yield diminishing returns. Fortunately, advanced multi-omics and computational approaches present powerful solutions to these challenges. This review highlights innovative methodologies that integrate metabolomics, genomics, transcriptomics, and proteomics with bioinformatics and analytical chemistry to accelerate NP discovery. For instance, untargeted metabolomics platforms like high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) and Global Natural Products Social (GNPS) molecular networking allow for comprehensive profiling of new compounds, while targeted isotope-labeling strategies enhance this process. Additionally, genome and metagenome mining tools such as antibiotics and secondary metabolite analysis shell (antiSMASH), Deep Biosynthetic Gene Cluster (DeepBGC), and Pipeline for Reconstructing Integrated Syntheses of Metabolites (PRISM) quickly identify biosynthetic gene clusters (BGCs) in both cultured and uncultured organisms, often using heterologous expression to validate products. Transcriptomic analyses, including RNA sequencing (RNA-seq), co-expression networks, and fluxomics, help clarify how pathways are regulated, while quantitative proteomics techniques like tandem mass tags/isobaric tags for relative and absolute quantitation (TMT/iTRAQ) and label-free methods, along with chemoproteomics approaches such as cellular thermal shift assay and thermal proteome profiling (TPP), uncover molecular targets and their mechanisms of action. This review also places significant emphasis on the role of artificial intelligence (AI) and machine learning (ML) in integrating multi-omics data, spanning activities from constructing gene-metabolite correlation networks to leveraging knowledge graphs and graph neural networks for data fusion and functional prediction. Finally, this review concludes by discussing the synergistic benefits of multi-omics for natural-product discovery, addressing current technical challenges, and exploring future directions toward high-throughput, intelligent data integration for next-generation NP research.

Biological Products↗

PubMed2025

Genetic risk factors modulate the association between physical activity and colorectal cancer.

BACKGROUND: Physical activity (PA) is an established protective factor for colorectal cancer (CRC), but it is unclear if genetic variants modify this effect. To investigate this possibility, we conducted a genome-wide gene-PA interaction analysis. METHODS: Using logistic regression and two-step and joint tests, we analyzed interactions between common genetic variants across the genome and PA in relation to CRC risk. Self-reported PA levels were categorized as active (≥ 8.75 MET-h/wk) vs. inactive (< 8.75 MET-h/wk) and as study- and sex-specific quartiles of activity. RESULTS: PA had an overall protective effect on CRC (OR [active vs. inactive] = 0.85; 95%CI = 0.81-0.90). The two-step GxE method identified an interaction between rs4779584, an intergenic variant near the GREM1 and SCG5 genes, and PA for CRC risk (p-interaction = 2.6×10- 8). Stratification by genotype at this locus showed a significant reduction in CRC risk by 20% in active vs. inactive participants with the CC genotype (OR = 0.80; 95%CI = 0.75-0.85), but no significant PA-CRC association among CT or TT carriers. When PA was modeled as quartiles, the 1-d.f. GxE test identified that rs56906466, an intergenic variant near the KCNG1 gene, modified the association between PA and CRC (p-interaction = 3.5×10- 8). Stratification at this locus showed that increase in PA (highest vs. lowest quartile) was associated with a lower CRC risk solely among TT carriers (OR = 0.77; 95%CI = 0.72-0.82). CONCLUSIONS: In summary, we identified two genetic variants that modified the association between PA and CRC risk. One of them, related to GREM1 and SCG5, suggests that the bone morphogenetic protein (BMP)-related, inflammatory, and/or insulin signaling pathways may be associated with the protective influence of PA on colorectal carcinogenesis.

GWAS↗

PubMed2025

An advanced cytosine base editor enabled the generation of cattle with a stop codon in the β-lactoglobulin gene.

β-Lactoglobulin (BLG) is an allergen present in milk that can induce an acute immune response in certain individuals. The successful use of cytosine base editors (CBEs) can introduce stop codons into premature mRNA, thereby generating animals with disrupted genes that negatively regulate target traits. In this study, we employed a CBE system to target the major milk allergen BLG in bovine embryos, mammary epithelial cells, and live cattle. First, the precise single-base editing of the BLG gene in bovine embryos was achieved by designing an effective sgRNA to induce a c.61C > T substitution in the coding region, converting codon 21Gln (p.21Gln) to a premature stop codon. Sanger sequencing revealed an editing efficiency of 83.3% (20 out of 24 embryos), including two homozygous edits. Second, a bovine mammary epithelial cell line harboring BLG edits was constructed using the same CBE system. Sequencing showed that the designed sgRNA1 enabled the simultaneous conversion of three consecutive cytosines (c.59-61CCC > TTT) to thymines. At position c.61, single-cell clones exhibited monoallelic or biallelic editing (BLGc.61C > T), with monoallelic edits at positions c.59 and c.60 (CC > TT). Gene expression analysis confirmed that the BLGc.61C > T mutation effectively suppressed BLG expression at both the mRNA and protein levels, even in monoallelically edited cells. Finally, we successfully generated a heterozygous BLGc.61C > T single-base-edited dairy cow that despite its heterozygosity, showed significantly reduced BLG expression in the mammary epithelial cells and milk. Collectively, this study demonstrates the feasibility of using CBEs to disrupt BLG expression in dairy cows and provides a foundation for application in generating hypoallergenic dairy products.

Animals↗

PubMed2024

Bidirectional association between abnormal cardiac conditions and epilepsy: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies have consistently indicated a significant correlation between abnormal cardiac conditions and epilepsy. However, the association and direction of this relationship remain a subject of debate. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to investigate the association between abnormal cardiac conditions and epilepsy. METHODS: Instrumental variables, represented by single nucleotide polymorphisms (SNPs) associated with epilepsy and various abnormal cardiac conditions, were derived from large-scale genome-wide association studies databases, including FinnGen and UK Biobank. Bidirectional MR analysis was conducted to estimate the association between epilepsy and abnormal cardiac conditions. Sensitivity analyses were performed using MR-Egger, weighted median, Inverse Variance Weighted, and MR pleiotropy residual sum and outlier methods. RESULTS: The forward MR analysis suggested a potential positive effect of atrial fibrillation and flutter (AF) and valvular heart diseases (VHD) on the risk of epilepsy. Conversely, the reverse MR analysis indicated that epilepsy might increase the susceptibility to AF, VHD, and heart failure. CONCLUSION: The findings support a bidirectional relationship between AF, VHD, and epilepsy, indicating that AF and VHD can elevate the risk of developing epilepsy, while epilepsy, in turn, can also increase the risk of developing AF and VHD. Furthermore, the study suggest that epilepsy may contribute to the development of heart failure. These results underscore the importance of screening for cardiac abnormalities in patients with epilepsy and vice versa, to better understand their clinical significance and potential as modifiable risk factors.

Humans↗

PubMed2024

Identifying inversions with breakpoints in the Dystrophin gene through long-read sequencing: report of two cases.

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is an X-linked disorder caused by mutations in the DMD gene, with large deletions being the most common type of mutation. Inversions involving the DMD gene are a less frequent cause of the disorder, largely because they often evade detection by standard diagnostic methods such as multiplex ligation probe amplification (MLPA) and whole exome sequencing (WES). CASE PRESENTATION: Our research identified two intrachromosomal inversions involving the dystrophin gene in two unrelated families through Long-read sequencing (LRS). These variants were subsequently confirmed via Sanger sequencing. The first case involved a pericentric inversion extending from DMD intron 47 to Xq27.3. The second case featured a paracentric inversion between DMD intron 42 and Xp21.1, inherited from the mother. In both cases, simple repeat sequences (SRS) were present at the breakpoints of these inversions. CONCLUSIONS: Our findings demonstrate that LRS is an effective tool for detecting atypical mutations. The identification of SRS at the breakpoints in DMD patients enhances our understanding of the mechanisms underlying structural variations, thereby facilitating the exploration of potential treatments.

Humans↗