Lymphocystis disease viruses (LCDVs), members of the Lymphocystivirus genus of the Iridoviridae family, infect various freshwater and marine fish species. They cause the chronic disease lymphocystis, which is non-fatal, but substantially reduces the commercial value of the infected fish. To date, four genotypes of LCDV (LCDV1–4) have been identified, all of which encode the viral homologue of B-cell lymphoma 2 (Bcl-2), a key inhibitor of apoptosis. In this study, we performed biochemical and structural analyses of LCDV2 Bcl-2. Binding assays revealed that LCDV2 Bcl-2 exhibits binding selectivity toward BH3 domain-containing zebrafish proteins. It interacted with zBaxA and zNoxa, but not with zBaxB, zBid, or zBeclin 1, distinguishing it from mammalian and herpesviral Bcl-2 proteins. Subsequent structural determination of LCDV2 Bcl-2 in complex with the BH3 domain of zBaxA demonstrated that they interact in a canonical manner, primarily mediated by the BH3 consensus motif residues of zBaxA. In addition, a subpocket formed by two phenylalanine residues in LCDV2 Bcl-2 plays a key role in determining binding selectivity.

Actinobacillus pleuropneumoniae (APP) is the etiological agent of porcine pleuropneumoniae (PP), a high contagious respiratory disease with significant impact on the swine industry in both clinically and economically. Despite of the several attempts to control APP, the emergence of novel serotypes and antimicrobial resistance (AMR) strains highlights the importance of monitoring the genetic characteristics of APP at single nucleotide level. Despite the importance of genomic surveillance of APP to develop effective control strategies, genetic information on the recent Korean isolates of APP is not available at whole genome level. Therefore, in this study, six APP strains were isolated from porcine lungs with characteristic lesions of PP from 2022 to 2024. And their whole genomic sequences, serotypes, virulence factors, and AMR traits were investigated using combined short- and long-read sequencing methods. In silico PCR serotyping identified the isolates as serotype 1, 7, and 15, while one isolate was non-typeable. Multiple AMR genes including Hinf_PBP3_BLA, Ecol_EFTu_PLV, tet(B), tet(O), tetR, sul2, aph(3'')-Ib, aph(6)-Id, and aph(3')-Ia were detected. Also, these genes were located with adjacent to mobile genetic elements, suggesting the possibility of horizontal gene transfer. Phylogenetic comparison with 40 global APP complete genomes, presented that Korean isolates were closely related with China and Switzerland strains. This study provides the whole genome sequences based genetic characterization on the recent Korean isolates of APP, and this study emphasizes that continuous monitoring of APP genomic variation to support effective control of porcine pleuropneumoniae.

Triterpenoids are natural products widely found in the plant kingdom and have various pharmacological effects such as anti-inflammatory, antioxidant and anti-tumour. However, the content of triterpenoids in medicinal plants is low, and it is difficult to purify and isolate them due to their complex structure. The efficient production of some triterpenoids in chassis organisms has been achieved by constructing a heterologous triterpenoid synthesis pathway in engineered strains such as yeast, modifying the key enzymes in the pathway, and adjusting the metabolism of yeast. Modification of key enzymes in the synthetic pathway is currently an effective strategy to enhance the heterologous synthesis of triterpenoids. This paper reviews the current research progress on the modification of key enzymes downstream in the synthetic pathway and the design of key enzymes around them to enhance triterpenoid production in five main areas: 1) increasing the supply of triterpenoid precursors; 2) inhibition of the natural sterol pathway; 3) fusion expression of related enzymes; 4) compartmentalisation of the metabolic pathway; and 5) tapping and enhancing the triterpenoid efflux pump. Finally, recent advances and applications of artificial intelligence (AI) in enzyme engineering and pathway design for triterpenoid biosynthesis are highlighted. Challenges and perspectives for further increasing the yield of triterpenoid synthesis in Saccharomyces cerevisiae are presented.

Based on the escalating challenge of drug-resistant Aspergillus fumigatus infections, this study developed a silver ion-loaded carboxymethyl chitosan (CMCh-Ag^⁺) nanocomposite as a potent antifungal agent. The composite was successfully synthesized and characterized, revealing distinct physicochemical properties, uniform dispersion, and confirmed coordination between CMCh and Ag^⁺. In vitro evaluations, including minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), growth curve, and plate spotting assays, demonstrated that CMCh-Ag^⁺ exhibited significantly superior antifungal efficacy against multiple A. fumigatus strains (including azole-resistant isolates) compared to CMCh or Ag^⁺ alone. In vivo experiments using a Galleria mellonella infection model confirmed the enhanced therapeutic effect and biocompatibility of CMCh-Ag^⁺. Investigations into the mechanism-related phenotypes revealed that CMCh-Ag^⁺ significantly removed fungal biofilm and was associated with a substantial accumulation of intracellular reactive oxygen species (ROS), correlating with fungal cell death. This research highlights the preliminary potential of CMCh Ag^⁺ as a candidate strategy to combat drug-resistant A. fumigatus infections, warranting further investigation in mammalian models to assess its clinical translational prospects.

I53-50 is a computationally designed, self-assembling protein nanoparticle (NP) that forms a stable icosahedral structure composed of 120 protein subunits coordinated through precise interfacial interactions. Through unique intelligent regulation, I53-50 exhibits sensitivity to environmental signals and display multimodal “nano-smart” properties. I53-50 has a variety of modifiable surface-active sites, which facilitates precise chemical modification, gene fusion, tag coupling, and other functionalizations, thereby promoting effective lymphatic uptake and optimizing the immune response. I53-50 NPs show great potential in vaccine development, drug delivery, and biomaterials, representing a model fusion of computational biology and nanomedicine and offering a versatile tool for precision medicine.

Following the global spread of SARS-CoV-2 Omicron (B.1.1.529), its subvariants KP.3.1.1, LP.8.1, and NB.1.8.1 disseminated worldwide. By April 2025, the epidemiological landscape of these subvariants had become distinct, with LP.8.1 emerging as the predominant variant, KP.3.1.1 persisting as a co-circulating variant under monitoring (VUM), and NB.1.8.1 exhibiting a significant increase in prevalence. Despite their epidemiological prominence, the functional consequences of spike mutations defining these emerging subvariants remain poorly understood. Here, we systematically dissected the entry properties conferred by their receptor-binding domain (RBD) mutations using a pseudovirus system. Our results demonstrate that all three subvariants exhibited substantially higher infectivity than ancestral Omicron. Unexpectedly, this enhanced infectivity occurred despite reduced ACE2 binding affinity. Rather, increased viral entry consistently correlated with elevated spike cleavage efficiency and fusogenicity, suggesting a compensatory evolutionary strategy in which enhanced spike processing and fusion contribute to enhanced entry despite reduced receptor engagement. These findings provide a virological explanation for the accelerated global spread of these subvariants and highlight the importance of monitoring functional shifts in spike-mediated entry that may influence SARS-CoV-2 transmission dynamics.

This study presents the first investigation of acetyl-11-keto-β-boswellic acid (AKBA)’s anti-human cytomegalovirus (HCMV) activity in vitro and elucidates its underlying mechanisms. In HCMV Towne strain-infected WI-38 cells, AKBA (1-12 μM) exhibited negligible cytotoxicity while significantly suppressing virus-induced cytopathic effects (CPE) at 6–10 μM, with dose-dependent reduction of viral proteins (IE1/2 and p52) expression, viral DNA copy number (UL123, UL44, and UL32), and infectious viral progeny titer (TCID₅₀). Time-of-addition experiments demonstrated the primary antiviral activity of AKBA during post-entry phase, along with direct virion inactivation. Transcriptome analysis revealed that AKBA significantly downregulated the expression of the host factor NR4A1 induced by HCMV, a finding further validated by Western blotting. Further gene knockdown experiments confirmed that silencing NR4A1 significantly reduced the expression of viral proteins IE1/2, thereby validating NR4A1 as a key host factor for HCMV infection. These findings indicate that AKBA has a potent and dose-dependent inhibitory effect on HCMV replication in WI-38 cells, and proves that this effect is mediated through two different mechanisms: one is the downregulation of the expression of the key host factor NR4A1, and the other is the direct inactivation of HCMV viral particles.

Phytoplasmas are wall-less obligate parasites of plants and insects. Several phytoplasma strains within the Peanut Witches’ Broom (PWB; 16SrII) group are associated with significant disease losses across diverse crops and weeds. We present complete, single contig genome assemblies for two Indian parthenium phyllody strains, ‘Candidatus Phytoplasma asiaticum’ PR34 and ‘Ca. P. australasiaticum’ PR08, generated through host DNA depletion and hybrid Illumina–Nanopore sequencing. Both genomes display characteristic features of reductive evolution (∼614 kb and 589 kb, respectively) but show notable differences from previously sequenced PWB phytoplasmas. In contrast to most of PMU-rich phytoplasma genomes, neither PR34 nor PR08 retains intact Potential Mobile Units. Instead, both harbor numerous open reading frames encoding group II intron reverse transcriptase/ maturase proteins, predominantly of the mitochondrial-like type, with PR34 containing 52 and PR08 28 such loci that together constitute > 4% of each genome. These observations support the hypothesis that intron-associated processes may contribute to genome variability in the absence of canonical PMUs. Comparative analyses support the classification of PR34 as a distinct species within the PWB complex and reveal both conserved Sec-dependent effectors (SAP05, SAP11, and SAP54/PHYL1) and lineage-specific secreted proteins with predicted nuclear localization. Additional retained features include functional sodA genes and multiple truncated HlyB-like transporters. Collectively, these high-quality genomes illustrate a genomic configuration in which extensive genome reduction and loss of PMUs coexist with the retention of core virulence factors and an expanded repertoire of group II introns, providing a framework for future investigation of genome plasticity in phytoplasmas.

Synthetic rescue (SR) describes a genetic interaction in which the deleterious effect of a primary mutation is compensated by a second mutation, restoring cellular function or viability. In Saccharomyces cerevisiae, SR complements synthetic lethality (SL) by revealing compensatory mechanisms that maintain essential biological processes. Classical studies established SR as a fundamental principle of genetic robustness in yeast. Subsequent development of high-throughput genetic tools, including Synthetic Genetic Array (SGA), Epistatic Miniarray Profile (E-MAP), and CRISPR interference (CRISPRi), has enabled systematic identification of SR interactions across pathways of genome maintenance, proteostasis, and metabolism. Integration of these experimental datasets with computational and network-based analyses has transformed SR research from descriptive genetics into a predictive framework. Databases such as BioGRID, TheCellMap, and Mslar further support SR inference and link yeast genetic networks to human disease models. Understanding SR has important translational implications. The same compensatory logic that restores viability in yeast can explain therapeutic resistance in cancer cells. Together, these insights reveal SR as a powerful concept connecting microbial genetics with systems medicine, emphasizing that robustness and resilience are dynamic properties of living systems.

Two novel bacterial species, designated as CJ85^T and CJ88^T, were isolated from the agricultural soil and the Han River, South Korea, respectively. Cells of both strains were Gram-staining-positive, short rod-shaped, non-motile, and yellow-pigmented. Strain CJ85^T exhibited optimal growth in tryptic soy broth at 37°C and pH 7.0 in the absence of NaCl. Strain CJ88^T showed optimal growth in lysogeny broth at 30°C and pH 7.0 in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CJ85^T belonged to the genus Paramicrobacterium, showing the highest sequence similarity to Paramicrobacterium fandaimingii HY82^T (97.6%). Strain CJ88^T was assigned to the genus Microbacterium, with the highest sequence similarity to Microbacterium azadirachtae DSM 23848^T (98.5%). The DNA G + C content was 64.8% for strain CJ85^T and 70.5% for strain CJ88^T. The genome-based analyses, including phylogenomic tree, digital DNA-DNA hybridization, and average nucleotide identity, clearly indicated that these strains represent novel species within their respective genera. The major fatty acids of both strains were anteiso-C_15:0, anteiso-C_17:0, and iso-C_16:0. Based on the polyphasic taxonomy study, strains CJ85^T and CJ88^T represent novel species of the genera Paramicrobacterium and Microbacterium, respectively, for which names Paramicrobacterium salitolerans sp. nov. and Microbacterium fluminis sp. nov. are proposed. The type strains CJ85^T (= KACC 23064^T = JCM 36217^T) and CJ88^T (= KACC 24080^T = JCM 38050^T).