Biomedical subjects

Bowen Li

Publications and source records attributed to Bowen Li.

6 recordsLinked to original sources

PubMed2026

Genome-wide screening and functional analysis of protein glycosylation-related genes involved in tomato fruit ripening.

Protein glycosylation, an essential co- and post-translational modification, plays critical roles in plant growth, development, and stress responses. However, its functional role in tomato fruit ripening has not been extensively investigated. Here, key protein glycosylation-related genes involved in tomato fruit ripening were identified by genome-wide screen and subsequently functional characterization. First, a dataset comprising 242 glycosylation-related proteins was established based on Gene Ontology annotations in tomato, combined with sequence homology to protein glycosylation-related proteins from Arabidopsis thaliana and Homo sapiens. Then, Subsequently, 28 genes encoding highly expressed glycosylation-related proteins (RPKM > 30) at the breaker (BR) stage were selected for functional screening, and subsequently 6 genes were identified as regulators of fruit ripening by method of virus-induced gene silencing (VIGS). Among them, Solyc03g098600 (STT3B), Solyc01g109410 (OST48), Solyc04g082670 (RPN1), and Solyc08g076460 (DAD1) functioned as positive regulators of tomato fruit ripening, whereas Solyc04g005340 (UAM2) and Solyc08g075340 (XEG113), acted as negative regulators. The expression of these genes responded dynamically to multiple ripening-related cues, including temperature, light, ethylene, and transcription factors. Furthermore, silencing of these genes individually affected the expression of genes involved in fruit ripening, including ethylene biosynthesis genes (ACS2, ACS4, ACO1, and ACO3), ripening-associated transcription factors (RIN, NOR, NOR-LIKE1, FUL1, and FUL2), and the key gene (PSY1) of lycopene biosynthesis pathway. Collectively, these findings demonstrate that protein glycosylation plays an important role in tomato fruit ripening by modulating ethylene signaling, ripening-associated transcriptional regulation, and lycopene biosynthesis.

Fruit ripening↗

PubMed2026

Emergence of cefiderocol resistance in carbapenem-resistant Escherichia coli ST167 prior to clinical use: A multifactored resistance landscape.

OBJECTIVES: Cefiderocol is a novel siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria. Here, we reported the prevalence and mechanisms of cefiderocol resistance in carbapenem-resistant Escherichia coli (CREC) in China before its clinical use. METHODS: A total of 443 non-duplicate CREC isolates collected from 67 hospitals in China (2013-2021) underwent antimicrobial susceptibility testing according to CLSI guidelines. Whole-genome sequencing, transcriptomic analysis, siderophore quantification, and targeted genetic manipulation were performed to investigate the underlying resistance mechanisms. RESULTS: Among the 443 CREC isolates, 102 (23.0%) were resistant to cefiderocol, and 34 (7.6%) showed intermediate susceptibility. Multivariable logistic regression identified ST167 lineage (OR, 3.05; 95% CI, 1.12-8.29; P = 0.028), blaNDM-5 carriage (OR, 9.04; 95% CI, 2.96-27.57; P < 0.001), and cirA truncation (OR, 49.56; 95% CI, 20.33-120.79; P < 0.001) as independent factors associated with cefiderocol resistance. Among ST167 isolates, cefiderocol-resistant isolates showed increased yersiniabactin carriage and siderophore production but comparable TonB-dependent transporter expression profiles. Phylogenetic analysis revealed that cefiderocol-resistant ST167 isolates clustered into a distinct subclade enriched with resistance-associated determinants, including a recurrent FhuA P50S substitution detected in 59/64 (92.2%) resistant isolates. Functional assays showed that the P50S substitution increased cefiderocol minimum inhibitory concentration (0.032-0.125 µg/mL), particularly in an NDM-5-producing background (0.032-0.5 µg/mL). CONCLUSIONS: Cefiderocol resistance is highly prevalent among high-risk ST167 CREC isolates before the clinical introduction of cefiderocol in China, highlighting the need for continued surveillance of this epidemic lineage. Cefiderocol resistance is mediated by multiple resistance determinants, and we identify the recurrent FhuA P50S substitution as a novel contributor to reduced cefiderocol susceptibility.

Antimicrobial resistance↗

PubMed2025

The association between milk fat intake and atopic dermatitis: A study based on NHANES from 1999 to 2006 and Mendelian randomization.

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease imposing significant global burden. While dietary factors are implicated in AD, the relationship between milk fat intake and AD risk remains unclear, particularly regarding optimal fat levels. This study aimed to investigate the association between milk fat intake and AD risk in adults. Relevant data (included a total of 9760 participants) from National Health and Nutrition Examination Survey between 1999 and 2006 were selected, and the relationship between milk fat intake and AD was assessed using weighted multifactorial logistic regression. Subsequently, a 2-sample Mendelian randomization (MR) study was conducted using the summary statistics of genome-wide association studies, and the causal relationship between the 2 was verified through inverse variance weighting, Bayesian weighted MR, and other supplementary MR methods. Weighted multifactorial logistic regression analysis adjusted for other covariates showed that, compared with the intake of full-fat milk, the intake of 1% fat milk (M3: odds ratio [OR]: 1.476, 95% confidence interval [CI]: 1.157-1.874, P = .005), nonfat milk (M3: OR: 1.578, 95% CI: 1.288-1.930, P < .001), as well as for milk abstainers (M3: OR: 1.303, 95% CI: 1.061-1.600, P = .025) increased the risk of AD. MR analysis further validated a significant inverse association between milk fat intake and AD risk, with both primary methods demonstrating statistical significance (P < .05) and no significant pleiotropy or heterogeneity detected in sensitivity analyses. Compared with the population consuming full-fat milk, the risk of AD may be higher in American adults consuming 1% fat milk, nonfat milk, and milk abstainers.

Humans↗

PubMed2025

Largest-Scale Genomic Resource Reconstructing the Genetic Origin, Population Structure, and Biological Adaptations of the Hui People.

Historical and archaeological records indicate that the Maritime and Land Silk Roads played a pivotal role in facilitating Trans-Eurasian migrations and cultural exchanges. However, the extent to which population movements or the spread of ideas shape Chinese Hui populations remains debated. We present the largest genomic resource to date, including 2,280 Hui individuals sequenced or genotyped from 30 diverse regions, to examine the genetic origins, population structure, and biological adaptations of this underrepresented group in global human genome research. We identified a detailed population structure characterized by five distinct genetic lineages of the Hui, influenced by geography and varying gene flow. The admixture history and demographic events suggest that the northwestern and northern Hui lineages emerged from demic diffusion during the Tang and Yuan Dynasties via the Land Silk Road. In contrast, the southern and island Hui lineages reflect cultural diffusion along the Maritime Silk Road, while the mixed southern-northern lineage likely developed through a combination of demic and cultural diffusion. Our findings support a hybrid model for Hui formation, indicating that both demographic processes and sociocultural transmissions contributed to their population history. We identified east-west highly differentiated variants and pre- and post-admixture adaptations in Hui genomes, demonstrating that admixture-driven adaptive or neutral variants impacted susceptibility to cardiovascular diseases and immune- and diet-related traits. These adaptive signatures include post-admixture signals of SLC24A5 and ECHDC1 in the Hui, as well as pre-admixture signals of the HLA region, BCL2A1, and KCNH8 in the East Asian source. Overall, our study suggests that Han-related genetic components helped the Hui population rapidly adapt to new local environments. Additionally, the frequency spectrum of clinically essential variants differed significantly between Hui and Han individuals, emphasizing the importance of including underrepresented populations in genomic research to promote health equity.

Humans↗

PubMed2025

Strain-Promoted mRNA Transdermal Delivery by Lipoic Lipid Nanoparticles for Therapeutic Skin Genome Editing.

Lipid nanoparticle (LNP)-mRNA formulations have revolutionized the field of nucleic acid therapeutics, yet their broader clinical application is constrained by inflammatory side effects and oxidative stress, particularly in the context of inflammatory diseases. Herein, we report the rational design and synthesis of a lipoic acid-based ionizable lipid library to address these limitations. By leveraging the antioxidant properties and thiol-mediated uptake potential of lipoic acid, we identified LA-A2B2CD3 as an optimal candidate through a structure-activity relationship study and design of experiment (DOE) optimization. LA-A2B2CD3 LNPs exhibited superior reactive oxygen species scavenging, enhanced mRNA translation, and reduced inflammatory cytokine production in vitro and in vivo. Mechanistic studies revealed that the efficient cellular uptake and the transdermal delivery capacity of LA-A2B2CD3 heavily rely on the reducible disulfide ring of lipoic acid. Application of LA-A2B2CD3 LNPs for the localized transdermal delivery of Cas9 mRNA and CD93 sgRNA in a murine model of psoriasis resulted in effective CD93 genome editing and the inhibition of the CD93-p38 MAPK-AKT-SMAD2/3 pathway, leading to significant therapeutic improvement. This work presents a robust, biocompatible LNP platform with minimized immunogenicity and strong potential for genome-editing therapies in inflammatory conditions, offering a transformative approach for the mRNA-based treatment of skin and other inflammation-related disorders.

Animals↗

PubMed2025

Aplf/Dna2 variants drive chromosomal fission and accelerate speciation in zokors.

Chromosomal fissions and fusions are common, yet the molecular mechanisms and implications in speciation remain poorly understood. Here, we confirm a fission event in one zokor species through multiple-omics and functional analyses. We traced this event to a mutation in a splicing enhancer of the DNA repair gene Aplf in the fission-bearing species, which caused exon skipping and produced a truncated protein that disrupted DNA repair. An intronic deletion in Dna2, known to facilitate neo-telomere formation when knocked out, reduced gene activity. These variants collectively drove chromosomal fission in this zokor species. The newly formed chromosome became fixed due to carrying essential genes and strong selective pressure. While geographic isolation likely initiated the divergence of this species and the sister one, the fission event and associated decline at the chromosome level in gene flow probably exacerbated the speciation process. Our work elucidates the genetic basis of chromosomal fission and underscores its role in speciation dynamics.

Multiomics↗