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Biomedical subjects

Qiang Wang

Publications and source records attributed to Qiang Wang.

11 recordsLinked to original sources
PubMed2026

Antibacterial activity and mechanistic insights of Lucilia illustris antimicrobial peptide Cecropin A2 against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) poses a serious public health threat due to multidrug resistance and biofilm formation. This study investigated the antibacterial mechanisms of the antimicrobial peptide, Cecropin A2 (CA2), against P. aeruginosa. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CA2 against P. aeruginosa ATCC 9027 (PA ATCC 9027) were determined by broth microdilution. Antibacterial activity was evaluated using growth curves and time-kill assays. The mechanism was explored by assessing membrane integrity (outer/inner membrane permeability, SEM, and fluorescence microscopy), and intracellular responses (ATP, SDH activity, and ROS). Biofilm effects were assessed by crystal violet staining (biomass) and viable cell counting (biofilm-embedded bacteria). The MIC and MBC of CA2 against PA ATCC 9027 were 37.34 μM and 74.68 μM, respectively. CA2 exhibited moderate antibacterial activity against PA ATCC 9027. Scanning electron microscopy (SEM) revealed marked morphological damage after treatment. CA2 affected intracellular metabolism, potentially interacted with genomic DNA, and reduced biofilm biomass. Cecropin A2 exhibits concentration-dependent in vitro antibacterial activity against P. aeruginosa ATCC 9027, providing mechanistic insights and a theoretical basis for the development of alternative antimicrobial strategies.

Antimicrobial activity↗
PubMed2026

Mechanism of Shoutai Wan against recurrent spontaneous abortion: regulation of decidual vascular remodeling via ERβ-ANGPT2 signaling axis.

Shoutai Wan (STW), a classic traditional Chinese medicine formula used to tonify the kidney and prevent miscarriage, has been widely applied in the clinical management of recurrent spontaneous abortion (RSA). Increasing clinical evidence supports its efficacy in reducing miscarriage rates and improving pregnancy outcomes. However, the molecular basis by which STW alleviates defective decidual vascular remodeling in unexplained RSA remains insufficiently understood. Clinically, decidual ERβ and ANGPT2 expression, as well as serum estradiol, ANGPT2 and VEGFA levels were significantly decreased in RSA patients, accompanied by reduced decidual microvascular density. Furthermore, ERβ expression was positively correlated with ANGPT2 and microvascular density. In vivo, STW dose-dependently reduced embryo loss in RSA mice, repaired the damaged decidual-placental interface structure, and improved vascular maturation, structural stability and endothelial-pericyte ultrastructural connections. Mechanistically, STW upregulated ERβ expression. We demonstrated that ERβ binds to the ANGPT2 promoter, suggesting transcriptional upregulation of ANGPT2, thereby activating Tie2 and the downstream PI3K/AKT pathway and increasing NO and VEGFA secretion. In vitro, hypoxia inhibited ERβ nuclear translocation and ANGPT2 secretion in mDSCs, while STW-containing serum reversed these abnormalities. ERβ knockdown impaired the pro-angiogenic capacity of mDSCs, which was partially rescued by exogenous ANGPT2 supplementation. Network pharmacology predicted that STW targets were mainly enriched in PI3K-Akt, estrogen, VEGF and angiogenesis-related pathways. Transcriptomic GSEA further revealed that the gene signatures of angiogenesis and PI3K-Akt signaling were markedly suppressed in the RSA model, and STW treatment significantly normalized these transcriptional signatures.

Female↗
PubMed2026

Discovery of antimicrobial peptides from incomplete biosynthetic gene clusters to combat multidrug-resistant bacteria.

The escalating crisis of multidrug-resistant bacteria necessitates innovative antibiotic discovery platforms. Conventional antimicrobial peptide (AMP) mining often relies on complete biosynthetic gene clusters (BGCs), leaving fragmented genomic resources underexplored. Here, we present an evolution-inspired approach to reconstruct and predict AMPs from partial BGCs. Applying this strategy to 954 Paenibacillus genomes identifies five polymyxin-like peptides, NP001-NP005, with broad in vitro activity. Crucially, in murine models of polymyxin-resistant infection, NP001 reduced bacterial burdens by up to 1,000-fold in a thigh infection model and improved survival (50% vs. 0%) in a lethal peritonitis model. Structural simulations and biophysical assays revealed that NP001 maintains high affinity for bacterial membranes and effectively binds to MCR-1-modified lipid A, a key colistin-resistance mechanism. Moreover, Leu at position 10 of NP001 plays a key role in antibacterial activity against MCR-1-resistant bacteria. Our work establishes a generalizable framework for AMP discovery and introduces a promising therapeutic candidate, NP001, which effectively counteracts polymyxin-resistant pathogens.

Multigene Family↗
PubMed2026

cPRC1.2 and CTCF-mediated transition from poised to active chromatin loops at bivalent genes.

Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identify an unexpected role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2) in activating bivalent genes. Hi-C revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them poised for activation. Pcgf2 deletion disrupts cPRC1.2 loops and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identify CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, suggesting that PRC1 and CTCF cooperatively regulate chromatin loops. Through virtual 4C and other genomic analyses, we discover that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops. Our results suggest a novel mechanism by which pre-formed PRC1 loops at lineage-specific genes maintain a poised state for subsequent CTCF-mediated active loops and gene activation in cell fate transitions.

CCCTC-Binding Factor↗
PubMed2026

Genomic, virulent and phenotypic characterization of a cerebrospinal fluid-derived ST86-KL2 hypervirulent Klebsiella pneumoniae isolate from a patient with meningitis and diabetes mellitus.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) is an important cause of invasive community-acquired infection, particularly in individuals with diabetes mellitus. However, cerebrospinal fluid (CSF)-derived hvKP isolates, especially those belonging to the ST86-KL2 lineage, remain poorly characterized at the integrated clinical, genomic, and phenotypic levels. METHODS: A K. pneumoniae isolate, designated BP9811, was recovered from the CSF of a patient with meningitis and diabetes mellitus and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16 S rRNA sequencing. Antimicrobial susceptibility testing and whole-genome sequencing were performed to define its resistance, virulence, sequence type (ST), capsular type, and plasmid content. Virulence was evaluated using the Galleria mellonella infection model. In addition, interaction with human cerebral microvascular endothelial cells was preliminarily assessed using adhesion, gentamicin protection, and transmission electron microscopy assays, together with measurement of relative ompA transcription by reverse transcription-quantitative polymerase chain reaction. Comparative phylogenetic analyses were performed using publicly available CSF-derived and KL2 K. pneumoniae genomes. RESULTS: BP9811 was identified as a hypermucoviscous ST86-KL2 hvKP isolate that remained susceptible to all tested antimicrobial agents. Whole-genome sequencing revealed an IncHI1B virulence plasmid carrying canonical hvKP-associated determinants, including rmpA/rmpA2, peg-344, iucABCD, and iroBCD. In the Galleria mellonella model, BP9811 showed high virulence comparable to that of the hypervirulent reference strain NTUH-2044. In HCMEC/D3 cells, BP9811 exhibited increased adhesion and intracellular recovery under the tested conditions, and transmission electron microscopy confirmed bacterial internalization. BP9811 also showed higher ompA transcript levels than the control strain. Phylogenetic analysis indicated that BP9811 was genetically distinct from currently available CSF-derived isolates and occupied a related branch within the KL2 population. CONCLUSIONS: This study provides an integrated clinical, genomic, and phenotypic characterization of BP9811, a CSF-derived ST86-KL2 hvKP isolate recovered from a patient with meningitis and diabetes mellitus. BP9811 carried a canonical hvKP virulence plasmid, displayed marked virulence-associated phenotypes, and showed enhanced interaction with human cerebral microvascular endothelial cells in vitro under the tested conditions. These findings expand the limited isolate-level evidence on central nervous system-associated hvKP and provide a basis for future comparative and mechanistic studies.

Humans↗
PubMed2026

Schizophrenia and bipolar disorder: a comparative analysis of genetic and brain network connectivity.

BACKGROUND: Schizophrenia (SCZ) and bipolar disorder (BD) are severe psychiatric conditions with overlapping clinical presentations, genetic risk factors, and brain network dysfunction. Whether alterations in large-scale intrinsic brain networks reflect shared or disorder-specific genetic influences remains poorly understood. Clarifying this distinction is essential for refining etiological models and improving diagnostic precision. METHODS: Genome-wide inferred statistics (GWIS) were applied to decompose the genetic architecture of SCZ and BD into shared and unique components. Using resting-state network (RSN) data from the UK Biobank, functional connectivity (FC) and structural connectivity (SC) were extracted as neuroimaging phenotypes. Causal inference approaches were subsequently employed to infer potential directional relationships between brain network connectivity and each disorder. RESULTS: Analyses revealed both common and distinct patterns of brain network connectivity associated with SCZ and BD. Notably, SC within the default mode network (DMN) exhibited opposing effects across the two disorders, suggesting divergent structural underpinnings despite clinical overlap. Additionally, SC within the limbic network (LN) and frontotemporal control network demonstrated potential causal relationships with both conditions, implicating these circuits astransdiagnostic neural substrates. CONCLUSION: These findings illuminate the shared and disorder-specific genetic and neural architecture underlying SCZ and BD. Integrating genome-wide genetic methods with large-scale neuroimaging data offers a powerful framework for disentangling psychiatric comorbidity and may inform more targeted diagnostic criteria and individualized treatment strategies.

Humans↗
PubMed2026

Dock & design: engineering specificity for an alternative pimaradiene outcome with the ent-kaurene synthase from Bradyrhizobium japonicum.

The complexity of the reactions catalyzed by terpene synthases has hindered enzymatic engineering. In most cases such efforts result in non-specific product outcome, with the targeted compound being produced alongside others, hindering further use. Previous work with the structurally characterized ent-kaurene synthase from Bradyrhizobium japonicum (BjKS) identified a serine for alanine substitution (A167S) that led to premature deprotonation, yielding a pair of ent-pimaradiene double-bond isomers, with retrospective analysis by the TerDockin computational approach indicating that the introduced hydroxyl acts as a catalytic base for both. Here this route to 'short-circuiting' the BjKS catalyzed reaction for ent-pimaradiene production was further explored, with prospective application of TerDockin, via design-build-test cycles, enabling specific production of a novel pimaradiene isomer via introduction of a water molecule as the catalytic base. The resulting mutants, BjKS:F72S and particularly BjKS:F72Y/Y280S specifically yield the targeted ent-pimara-8,15-diene with reasonable catalytic efficiency, demonstrating the applicability of this computationally inexpensive approach to engineering terpene synthase product outcomes.

Journal Article↗
PubMed2025

FTDC1/2, oocyte-specific cofactors of DNMT1 required for epigenetic regulation and embryonic development.

The unique epigenetic patterns during gametogenesis and embryonic development indicate the existence of specialized methylation machinery. In the present study, we describe the discovery of two oocyte-specific cofactors of DNA methyltransferase 1 (DNMT1), encoded by uncharacterized genes, ferritin domain containing 1 and 2 (Ftdc1 and Ftdc2). Genetic ablation of Ftdc1 or Ftdc2 causes midgestation defects and female infertility. FTDC1 or FTDC2 depletion induces the progressive loss of DNA methylation including imprinted regions in early embryos. This loss correlates with a marked reduction in DNMT1 protein due to increased degradation, likely via the ubiquitin-proteasome pathway. Mechanistically, we find that FTDC1, FTDC2 and DNMT1 form a complex by direct interactions, thereby stabilizing each other. Surprisingly, knockout of Ftdc1 or Ftdc2 displayed stronger DNA demethylation phenotypes and earlier embryonic lethality than the Dnmt1-null mutant, implying their unique functions. These data suggest that FTDC1/2 are crucial players specifically involved in maintaining genomic methylation during embryogenesis, offering new insights into the epigenetic control of mammalian development.

DNA (Cytosine-5-)-Methyltransferase 1↗
PubMed2024

PRC1 and CTCF-Mediated Transition from Poised to Active Chromatin Loops Drives Bivalent Gene Activation.

Polycomb Repressive Complex 1 (PRC1) and CCCTC-binding factor (CTCF) are critical regulators of 3D chromatin architecture that influence cellular transcriptional programs. Spatial chromatin structures comprise conserved compartments, topologically associating domains (TADs), and dynamic, cell-type-specific chromatin loops. Although the role of CTCF in chromatin organization is well-known, the involvement of PRC1 is less understood. In this study, we identified an unexpected, essential role for the canonical Pcgf2-containing PRC1 complex (cPRC1.2), a known transcriptional repressor, in activating bivalent genes during differentiation. Our Hi-C analysis revealed that cPRC1.2 forms chromatin loops at bivalent promoters, rendering them silent yet poised for activation. Using mouse embryonic stem cells (ESCs) with CRISPR/Cas9-mediated gene editing, we found that the loss of Pcgf2, though not affecting the global level of H2AK119ub1, disrupts these cPRC1.2 loops in ESCs and impairs the transcriptional induction of crucial target genes necessary for neuronal differentiation. Furthermore, we identified CTCF enrichment at cPRC1.2 loop anchors and at Polycomb group (PcG) bodies, nuclear foci with concentrated PRC1 and its tethered chromatin domains, suggesting that PRC1 and CTCF cooperatively shape chromatin loop structures. Through virtual 4C and other genomic analyses, we discovered that establishing neuronal progenitor cell (NPC) identity involves a switch from cPRC1.2-mediated chromatin loops to CTCF-mediated active loops, enabling the expression of critical lineage-specific factors. This study uncovers a novel mechanism by which pre-formed PRC1 and CTCF loops at lineage-specific genes maintain a poised state for subsequent gene activation, advancing our understanding of the role of chromatin architecture in controlling cell fate transitions.

Journal Article↗
PubMed2024

Integrative Omics Reveals the Metabolic Patterns During Oocyte Growth.

Well-controlled metabolism is associated with high-quality oocytes and optimal development of a healthy embryo. However, the metabolic framework that controls mammalian oocyte growth remains unknown. In the present study, we comprehensively depict the temporal metabolic dynamics of mouse oocytes during in vivo growth through the integrated analysis of metabolomics and proteomics. Many novel metabolic features are discovered during this process. Of note, glycolysis is enhanced, and oxidative phosphorylation capacity is reduced in the growing oocytes, presenting a Warburg-like metabolic program. For nucleotide biosynthesis, the salvage pathway is markedly activated during oocyte growth, whereas the de novo pathway is evidently suppressed. Fatty acid synthesis and channeling into phosphoinositides are specifically elevated in oocytes accompanying primordial follicle activation; nevertheless, fatty acid oxidation is reduced in these oocytes simultaneously. Our data establish the metabolic landscape during in vivo oocyte growth and serve as a broad resource for probing mammalian oocyte metabolism.

Animals↗