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Dong Wang

Publications and source records attributed to Dong Wang.

7 recordsLinked to original sources
PubMed2026

Genomic prospecting and biochemical characterization of a novel thermostable 3-quinuclidinone reductase from hot spring metagenomes for efficient biocatalysis.

This study presents the discovery and characterization of a novel thermophilic 3-quinuclidinone reductase (ScQR) identified through metagenomic mining of hot spring environments. ScQR, a member of the short-chain dehydrogenase/reductase (SDR) superfamily, was heterologously expressed in Escherichia coli, and its catalytic properties were systematically characterized. The enzyme demonstrates exceptional thermal stability, retaining 86% of its activity after 48 hours at 70°C. Furthermore, K+ and Mg²+ ions significantly enhanced ScQR's activity at specific concentrations. Structural analysis revealed that ScQR adopts a typical SDR fold with a conserved catalytic triad (S141-Y155-K159), and it is NAD(H) dependent. Enzyme assays indicated that ScQR is highly stereoselective for (R)-3-quinuclidinol, with no activity against its enantiomer, (S)-3-quinuclidinol. The enzyme exhibits optimal activity at pH 9 and 85°C, making it a promising candidate for industrial applications requiring high thermal stability. Molecular dynamics simulations further revealed that ScQR preserves global structural integrity up to 360 K, whereas higher temperatures induce destabilization, predominantly in the C-terminal region and residues 95-100. In addition, structure-guided computational design enabled by LigandMPNN and UniKP yielded three ScQR variants with improved substrate affinity and catalytic efficiency while maintaining the overall fold and function. This work underscores the power of metagenomics with structure-driven protein design in discovering novel enzymes with unique catalytic properties from extreme environments and establishes ScQR as a promising biocatalyst for biotechnological and pharmaceutical applications.IMPORTANCEThis study reports the discovery of ScQR, a novel thermophilic 3-quinuclidinone reductase identified via metagenomic mining. ScQR represents one of the most heat-resistant members of the SDR superfamily discovered to date, maintaining 86% activity after 48 hours at 70°C. These findings establish ScQR as a robust biocatalyst for high-temperature pharmaceutical applications and demonstrate a scalable workflow for optimizing enzymes from extreme environments, offering significant value to the fields of biocatalysis and protein engineering.

computational design↗
PubMed2026

Genetic dissection of cardiac iron regulation using transcriptome network analysis and systems genetics in BXD mice.

Cardiac iron homeostasis is essential for myocardial energy metabolism and contractile function, yet the genetic and molecular mechanisms governing iron levels within the heart remain poorly understood. We used a systems genetics approach to dissect the transcriptional regulation of cardiac iron homeostasis. Myocardial iron level varies substantially across BXD strains (40-112 μg/g) and is under heritable genetic control (H2 = 0.38). Elevated cardiac iron is associated with reduced ventricular mass, increased ventricular ectopy, and prolonged atrioventricular conduction in the BXD population. Weighted gene co-expression network analysis of the BXD heart transcriptome identified a co-expression module that was significantly and negatively correlated with cardiac iron levels in both young and old BXD mice and enriched for pathways related to metabolic regulation, cyclic AMP (cAMP) signaling, circadian entrainment, and cardiovascular physiology. The module showed substantial overlap with a curated cardiac iron gene set, and cross-species enrichment analysis confirmed its conservation in human cardiomyopathy differentially expressed genes (enrichment ratio = 1.49; false discovery rate [FDR] = 0.0342). Quantitative trait locus (QTL) mapping of the first principal component of the overlapping module iron genes (n = 38), corroborated by individual gene mapping, identified trans-eQTL hotspots on multiple chromosomes, implicating Fcho2, Gcc2, and Rmdn1 as candidate upstream regulators operating through sequential steps of intracellular iron trafficking. Together, these findings establish a systems-level map of cardiac iron gene regulation, identify candidate genetic regulators, and provide a molecular framework linking disruption of iron-related transcriptional networks to structural and electrical cardiac dysfunction with implications for iron-related heart diseases.

BXD mouse population↗
PubMed2026

Flavonoid biosynthesis mediated by GmF3Hs contributes to drought tolerance in soybean.

Flavonoids are central to abiotic stress responses, yet the specific signaling roles and evolutionary dynamics of flavonoid biosynthetic intermediates in crop drought adaptation remain elusive. Here, we demonstrate that dihydrokaempferol (DHK) and dihydroquercetin (DHQ), specific intermediate products of the soybean flavanone 3-hydroxylases GmF3H1/2, function as potent signaling molecules that mitigate drought stress. Exogenous DHK/DHQ promoted abscisic acid-dependent stomatal closure and enhanced drought tolerance across diverse dicot species, including soybean and tobacco, highlighting a broadly conserved stress-mitigating signaling mechanism. CRISPR/Cas9-generated gmf3hs double mutants exhibited severe drought hypersensitivity due to compromised redox homeostasis and defective stomatal regulation, which could be specifically rescued by DHK/DHQ application. Furthermore, the loss of GmF3H triggered a distinct reproductive trade-off under stress, leading to increased pod initiation but severe filling defects. Multiomics network analysis revealed extensive rewiring of broader stress-responsive pathways and identified upstream transcription factors, among which GmPHL11 directly binds to and activates the GmF3H1 promoter; overexpression of GmPHL11 promoted DHK accumulation and enhanced drought stress tolerance in soybean hairy roots. Finally, population genomic analyses demonstrated that the GmF3H1H1 haplotype, which confers superior enzymatic activity and robust root growth under drought stress, might have undergone positive selection during soybean domestication. Collectively, our findings redefine the role of GmF3H-derived specific intermediates as potent signaling molecules, providing comprehensive mechanistic and evolutionary insights into flavonoid-mediated drought resilience, developmental trade-offs, and molecular breeding in crops.

Drought Resistance↗
PubMed2026

Genome-Wide Identification of NLP Family Genes in Cultivated Strawberry (Fragaria × ananassa Duch.) and Analysis of Their Expression Under Heat and Botrytis cinerea Stresses.

Nodule inception (NIN)-like proteins (NLPs) are plant-specific transcription factors regulating nutrient absorption, growth, and stress tolerance; however, their roles in stress responses remain largely uncharacterized. Cultivated strawberry (Fragaria × ananassa 'Camarosa') serves as an ideal model for dissecting the evolution and function of NLP genes. In this study, 37 FaNLP genes were identified genome-wide. Phylogenetic analysis classified them into three subfamilies, which are evenly distributed across seven chromosomes. Divergent exon-intron structures and conserved motif compositions suggest functional differentiation among FaNLPs. Quantitative real-time PCR (qRT-PCR) revealed distinct expression profiles under heat stress and Botrytis cinerea infection. Notably, FaNLPs were significantly more upregulated in the cultivar 'Shuxing' than in 'Benihoppe'. Heat stress inhibited photosynthesis and altered catalase activity (CAT), superoxide dismutase activities (SOD) and peroxidase activities (POD), whereas fungal infection enhanced chitinase activity in both cultivars. Comparative genomics with Arabidopsis and rice revealed strawberry-specific evolutionary patterns of NLPs. Subcellular localization prediction indicates that FaNLP proteins primarily localize to the nucleus, implying their potential roles as transcriptional regulators. This study links FaNLP sequence characteristics with stress response phenotypes, providing a foundation for elucidating NLP-mediated regulatory networks in strawberry. Future functional assays, including overexpression and knockout analyses, will further clarify the biological roles of FaNLPs.

Fragaria↗
PubMed2026

Integrated multi-omics profiling of amniotic fluid identifies predictive biomarkers for fetal growth restriction trajectories.

BACKGROUND: Fetal growth restriction (FGR) is a complex condition with highly heterogeneous clinical outcomes, making prenatal distinction between transient and persistent growth failure challenging. This study aims to identify amniotic fluid (AF) biomarkers capable of differentiating distinct FGR trajectories and characterizing persistent growth failure mechanisms. METHODS: Integrated proteomic and metabolomic profiling was performed on AF samples from transient FGR (n&#x2009;=&#x2009;11), persistent FGR (n&#x2009;=&#x2009;9), and healthy controls (n&#x2009;=&#x2009;13). Diagnostic and prognostic models were developed using multivariate analysis. Selected protein candidates were validated via ELISA in an independent cohort (n&#x2009;=&#x2009;69). RESULTS: Multi-omics analysis revealed distinct molecular signatures for FGR stratification. A two-protein diagnostic panel (PDGFA and phospho-STAT5A) achieved an AUC of 1.000 in the discovery stage and 0.780 in the external validation cohort. For prognostic assessment, a molecular signature including IREB2, HLA-C, and PLXNB2 accurately predicted persistent growth failure from transient recovery (AUC = 0.966). Cross-platform integration highlighted the mass spectrometry-derived WASHC2C as a central hub protein with a significant progressive increase across the control, transient, and persistent groups (p&#x2009;<&#x2009;0.001). CONCLUSIONS: This study establishes a multi-omics framework for prenatal FGR stratification. Our findings identify distinct molecular&#xa0;signatures reflecting&#xa0;the intrauterine environment and provide high-performance molecular tools for predicting divergent fetal growth trajectories to guide personalized clinical decision-making.

Humans↗
PubMed2026

Multiomics analysis reveals that senescent CXCL16+ macrophages promote lung adenocarcinoma progression through TGF-&#x3b2; signalling.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer and remains a leading cause of cancer-related mortality worldwide. Although, immunotherapy has become a cornerstone of first-line treatment, only 20-30% of patients achieve a durable clinical benefit, largely because of the complexity and heterogeneity of the tumour immune microenvironment. Emerging evidence indicates that cellular senescence, particularly within immune cells, contributes to tumour progression by impairing antitumour immunity; however, its mechanistic role in LUAD remains incompletely understood. METHODS: We performed an integrative multiomics analysis incorporating genome-wide association studies (GWASs), bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics to characterize immune heterogeneity in LUAD. Cellular senescence was validated by performing staining for senescence-associated &#x3b2;-galactosidase and the canonical markers p16 and p21. SHAP analysis was applied to evaluate the contribution of CXCL16+ macrophages. Functional roles were assessed using coculture assays, in vitro and in vivo tumour models, orthotopic tumour implantation, and multiplex immunofluorescence staining of clinical specimens. RESULTS: A summary data-based on Mendelian randomization analysis integrating GWAS and TCGA data identified CXCL16 as a senescence-associated gene that is causally linked to the LUAD risk. Single-cell RNA sequencing revealed that CXCL16 is predominantly expressed in macrophages, and the pseudotime analysis together with &#x3b2;-galactosidase staining confirmed its association with macrophage senescence. Spatial transcriptomics and immunofluorescence staining showed the marked enrichment of CXCL16+ macrophages in LUAD tissues. The cell-cell communication analysis further revealed a strong association between the number of CXCL16+ macrophages and the activation of the TGF-&#x3b2; signalling pathway within the tumour microenvironment. Functionally, CXCL16+ macrophages promoted LUAD progression via TGF-&#x3b2; signalling, as validated in vitro and in subcutaneous and orthotopic tumour models. Molecular dynamics simulations additionally suggested that LUAD patients with high levels of CXCL16+ macrophage infiltration may exhibit increased sensitivity to bosutinib. CONCLUSIONS: CXCL16 promotes macrophage senescence, and senescent CXCL16+ macrophages drive LUAD progression through TGF-&#x3b2; signalling. These findings identify CXCL16+ macrophages as a biologically and therapeutically relevant immune cell population, highlighting a potential target for precision intervention in LUAD.

Humans↗
PubMed2024

PSEUDO-RESPONSE REGULATOR 3b and transcription factor ABF3 modulate abscisic acid-dependent drought stress response in soybean.

The circadian system plays a pivotal role in facilitating the ability of crop plants to respond and adapt to fluctuations in their immediate environment effectively. Despite the increasing comprehension of PSEUDO-RESPONSE REGULATORs and their involvement in the regulation of diverse biological processes, including circadian rhythms, photoperiodic control of flowering, and responses to abiotic stress, the transcriptional networks associated with these factors in soybean (Glycine max (L.) Merr.) remain incompletely characterized. In this study, we provide empirical evidence highlighting the significance of GmPRR3b as a crucial mediator in regulating the circadian clock, drought stress response, and abscisic acid (ABA) signaling pathway in soybeans. A comprehensive analysis of DNA affinity purification sequencing and transcriptome data identified 795 putative target genes directly regulated by GmPRR3b. Among them, a total of 570 exhibited a significant correlation with the response to drought, and eight genes were involved in both the biosynthesis and signaling pathways of ABA. Notably, GmPRR3b played a pivotal role in the negative regulation of the drought response in soybeans by suppressing the expression of abscisic acid-responsive element-binding factor 3 (GmABF3). Additionally, the overexpression of GmABF3 exhibited an increased ability to tolerate drought conditions, and it also restored the hypersensitive phenotype of the GmPRR3b overexpressor. Consistently, studies on the manipulation of GmPRR3b gene expression and genome editing in plants revealed contrasting reactions to drought stress. The findings of our study collectively provide compelling evidence that emphasizes the significant contribution of the GmPRR3b-GmABF3 module in enhancing drought tolerance in soybean plants. Moreover, the transcriptional network of GmPRR3b provides valuable insights into the intricate interactions between this gene and the fundamental biological processes associated with plant adaptation to diverse environmental conditions.

Glycine max↗