(1) Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality and is characterized by pronounced inter- and intra-tumoral heterogeneity and therapy resistance. We aimed to define core transcriptional circuits that drive HCC malignancy and to delineate how these programs shape the tumor microenvironment (TME). (2) Methods: We integrated single-cell, spatial, and bulk transcriptomic datasets from public cohorts. (3) Results: We identified nine tumor-restricted transcription factors (TFs)—HTATIP2, HES6, ILF2, E2F1, MYBL2, DDIT3, FOXM1, HMGA1, and ETV4—whose expression and regulon activity associated with malignant phenotypes and poor survival. These TFs organize a progression axis from an early proliferative state (cluster C4) toward an invasive, metabolically adapted state (cluster C1) enriched for hypoxia, epithelial–mesenchymal transition (EMT), and inflammatory signaling. The C1 state remodeled the TME by establishing an immunosuppressive niche marked by expansion of T regulatory cells (Treg) and by accumulation of SPP1⁺ macrophages. These macrophages, recruited and polarized by C1 tumor cells, exhibited M2-like, pro-angiogenic, and immunosuppressive features and engaged epithelial, immune, and stromal partners via SPP1-CD44 and SPP1-integrin interactions. (4) Conclusions: In summary, a tumor-intrinsic TF network cooperates with SPP1⁺ macrophage signaling to promote a permissive microenvironment and HCC progression. This integrated axis highlights tractable vulnerabilities for therapeutic intervention.

Understanding the genetic basis of growth and moltism in silkworm (Bombyx mori) is essential for improving silk production efficiency and elucidating the mechanisms underlying developmental plasticity. Thus, this study aimed to establish a collection of 20 representative B. mori core strains and perform integrative genomic analyses combining genome-wide association studies (GWASs) and population-specific variant detection. A total of 5,293,831 high-confidence single-nucleotide variants (SNVs) were identified across the population, and GWAS revealed significant associations between specific genetic loci and four growth-related traits: larval weight at day 7 of the fifth instar, pupal weight, cocoon weight, and cocoon layer weight. Among these, two missense variants within the Cycb gene were significantly correlated with increased body weight at the late fifth instar stage, suggesting a potential role for this isoform in regulating cell-cycle-driven tissue expansion during rapid larval growth. Moreover, a population-based comparison identified 2803 trimolter-specific missense SNVs in 1440 genes, of which 109 were functionally annotated. Notably, homozygous variants were detected in key developmental regulators, such as MET1 and TOR1, implying potential alterations in juvenile hormone signaling and nutrient-dependent growth pathways that may contribute to the dominant trimolter phenotype. Although experimental validation remains necessary, these findings provide a genomic framework for understanding the molecular mechanisms underlying moltism variation and offer valuable resources for future silkworm genetic improvement.

Microcystis is a genus of cyanobacteria responsible for harmful algal blooms (HABs) in freshwater ecosystems, posing significant ecological and public health risks. Despite its importance, current genomic resources are heavily biased toward Microcystis aeruginosa, limiting comprehensive understanding of genomic diversity within the genus. In this study, we present the first complete genome sequences of two morphospecies, M. ichthyoblabe FBCC-A1114 and M. protocystis FBCC-A270. Using long-read sequencing, both genomes were assembled into single circular chromosomes of 5.84 Mb and 5.76 Mb, respectively. Phylogenetic analyses placed both strains within genospecies G, alongside M. aeruginosa and M. viridis. Comparative analysis of biosynthetic gene clusters revealed that, while most genospecies G members harbor aeruginosin, cyanobactin, and microviridin gene clusters, the two newly sequenced strains lack cyanobactin and microcystin clusters but retain the microginin cluster. Synteny analysis demonstrated high structural conservation between the two genomes, while notable structural variations were observed when compared with M. aeruginosa NIES-298. These findings reveal both functional and structural plasticity within the genospecies, suggesting ecotype diversification driven by environmental adaptation. The newly assembled genomes provide critical resources to refine classification frameworks and advance our understanding of Microcystis genomic diversity.

Dermacoccus barathri is the first reported pathogen within the Dermacoccus genus to cause a catheter-related bloodstream infection, which occurred in 2015. In this study, the complete genome assembly of Dermacoccus barathri was constructed, and the complete genome of Dermacoccus barathri FBCC-B549 consists of a single chromosome (3,137,745 bp) without plasmids. The constructed genome of D. barathri was compared with those of two closely related species within the Dermacoccus genus. D. barathri exhibited a pattern similar to Dermacoccus abyssi in terms of gene clusters and synteny analysis. Contrary to previous studies, biosynthetic gene cluster (BGC) analysis for predicting secondary metabolites revealed the presence of the LAP biosynthesis pathway in the complete genome of D. barathri, predicting the potential synthesis of the secondary metabolite plantazolicin. Furthermore, an analysis to investigate the potential pathogenicity of D. barathri did not reveal any antibiotic resistance genes; however, nine virulence factors were identified in the Virulence Factor Database (VFDB). According to these matching results in the VFDB, despite identifying a few factors involved in biofilm formation, further research is required to determine the actual impact of D. barathri on pathogenicity. The complete genome of D. barathri is expected to serve as a valuable resource for future studies on D. barathri, which currently lack sufficient genomic sequence information.