Background: Bungarus multicinctus, from which a classical Chinese medicine is produced, is known as the most venomous land snake in the world, but the chromatin organization and transcription factor activity during venom replenishment progress have not been explored yet. This study aimed to determine the roles of chromatin structure in toxin activity via bioinformatics and experimental validation. Methods: Chromosome conformation capture (Hi-C) analysis was used to examine interactions among chromosomes and identify different scales of chromatin during envenomation in B. multicinctus. Correlations between epigenetic modifications and chromatin structure were verified through ChIP-seq analysis. RNA-seq was used to validate the influence of variation in chromatin structure and gene expression levels on venom production and regulation. Results: Our results suggested that intra-chromosomal interactions are more intense than inter-chromosomal interactions among the control group, 3-day group of venom glands and muscles. Through this, we found that compartmental transition was correlated with chromatin interactions. Interestingly, the up-regulated genes in more compartmental switch regions reflect the function of toxin activity. Topologically associated domain (TAD) boundaries enriched with histone modifications are associated with different distributions of genes and the expression levels. Toxin-coding genes in the same loop are highly expressed, implying that the importance of epigenetic regulation during envenomination. On a smaller scale, the epigenetic markers affect transcriptional regulation by controlling the recruitment/inhibition of transcription initiation complexes. Conclusions: Chromatin structure and epigenetic modifications could play a vital status role in the mechanisms of venom regulation in B. multicinctus.

Quality control remains a challenge in traditional Chinese medicine (TCM). This study introduced a novel genetic-based quality control method for TCM. Genetic variations in ginseng were evaluated across whole-genome, chloroplast genome, and ITS2 DNA barcode dimensions. Significant genetic variations were found in whole-genome comparison, leading to the use of inter-simple sequence repeat markers to assess the genetic diversity of ginseng decoction pieces (PG), garden ginseng (GG), and ginseng under forest (FG). Fingerprints of ginseng samples revealed instability within some batches. These evaluations were transformed into information entropy to calculate the size of Hardy–Weinberg equilibrium population (HWEP). FG had significantly higher genetic and chemical minimum HWEP than GG (p < 0.05). Notably, a significant positive correlation was observed between the minimum HWEP for genetics and for chemistry (r = 0.857, p = 0.014). Genetic polymorphism analysis of ginseng has the potential to evaluate chemical quality consistency, offering a new method to ensure quality consistency in TCM.

Panax ginseng C. A. Mey., a precious traditional medicinal herb, demonstrates diverse pharmacological activities, including immunomodulation and anti-fatigue effects. However, prolonged cultivation has led to germplasm admixture and cultivar degeneration, resulting in inconsistent quality that severely compromises its medicinal value and industrial standardization. Therefore, establishing accurate and efficient germplasm evaluation tools is critical for ensuring the quality of P. ginseng medicinal materials. To integrate whole-genome sequencing and chemical fingerprinting for ginseng germplasm identification and quality consistency assessment. Chromosome-level genomes of ginseng from Jilin (JA) and Liaoning (FC) were assembled using PacBio HiFi, Illumina, and Hi-C technologies. Gene family identification and phylogenetic analysis were performed across 13 representative species. Using the JA genome as the reference, we constructed a pan-genome incorporating 7 ginseng genomes to dissect gene repertoire composition and structural variation distribution across ginseng populations. Population structure analysis with 76 individual ginseng samples revealed genetic diversity, and its integration with HPLC chemical fingerprints provided a joint assessment of quality consistency. We assembled two chromosome-level genomes and, through comparative genomics, revealed significant expansion of ginsenoside biosynthesis-related gene families and subgenome divergence. The core gene set accounted for 54.1% of the pan-genome, indicating high genetic conservation. SNP distribution patterns from population resequencing enabled the development of germplasm-specific molecular markers and a genetic-chemical integrated evaluation model. The molecular marker system and genetic-chemical joint assessment developed here provide reliable novel tools for germplasm identification and quality control, advancing standardization in the ginseng industry.