Fen Hu

Introduction: With the increasing prevalence of antibiotic resistance, the development of novel antibacterial materials is crucial to combat clinically relevant pathogens. This study comprehensively investigated the antibacterial properties and underlying mechanisms of a novel reversible photoacid-based crystalline material.Methods: The antibacterial efficacy of the material was evaluated against six clinically relevant pathogenic bacteria, including multidrug-resistant strains. The inhibition rates were determined, and scanning electron microscopy (SEM) was used to observe the effects on cell surface integrity. Transcriptomic analysis was conducted to elucidate the underlying antibacterial mechanisms.Results: The material exhibited broad-spectrum antibacterial activity, with higher sensitivity toward Gram-negative bacteria. Blue light irradiation significantly enhanced its antibacterial efficacy. SEM revealed that the material disrupted cell membrane integrity, leading to cell death. Transcriptomic analysis showed that the material inhibited bacterial protein synthesis, disrupted cell membrane protein synthesis, and downregulated oxidative stress-related genes, causing ROS accumulation and inhibiting cell growth.Discussion: These findings provide a theoretical basis for the potential clinical application of this material as a new antibacterial agent. The material’s ability to enhance antibacterial efficacy through light irradiation and its broad-spectrum activity suggest it could be a valuable tool in combating antibiotic-resistant pathogens. Future research should focus on further exploring the antibacterial mechanisms and evaluating the material’s safety and efficacy in clinical settings.

The control of Aedes albopictus (Skuse) (Diptera: Culicidae), a vector for several important viral diseases, is crucial for mitigating mosquito-borne diseases. This study focused on the Krüppel homolog 1 (Kr-h1) gene, a transcription factor in juvenile hormone (JH) signaling, which plays a pivotal role in inhibiting metamorphosis and promoting adult reproduction. We characterized Aedes albopictus Kr-h1(AalbKr-h1), identified its eight zinc finger domains, and confirmed its orthology among insects through phylogenetic analysis. Expression profiling across life stages showed high level of expression in eggs, late larvae, and adults, with minimal expression in pupae. In adults, AalbKr-h1 was most active in the fat body and ovaries. Exposing larvae to a JH analogue significantly upregulated AalbKr-h1 expression in both larval and adult stages. RNAi-mediated knockdown of Kr-h1 protein reduced egg reproduction, survival rate and gene expression levels. These results provide a solid foundation for further exploration of the function of the AalbKr-h1 gene and the potential development of novel strategies for mosquito control and prevention of mosquito-borne diseases. Graphical Abstract

Green-to-red photoconvertible fluorescent proteins (PCFPs) serve as key players in single-molecule localization super-resolution imaging. As an early engineered variant, mEos3.2 has limited applications, mostly due to its slow maturation rate. The recent advent of a novel variant, pcStar, obtained by the simple mutation of only three amino acids (D28E/L93M/N166G) in mEos3.2, exhibits significantly accelerated maturation and enhanced fluorescent brightness. This improvement represents an important advance in the field of biofluorescence by enabling early detection with reliable signals, essential for labelling dynamic biological processes. However, the mechanism underlying the significant improvement in fluorescent performance from mEos3.2 to pcStar remains elusive, preventing the rational design of more robust variants through mutagenesis. In this study, we determined the crystal structures of mEos3.2 and pcStar in their green states at atomic resolution and performed molecular-dynamics simulations to reveal significant divergences between the two proteins. Our structural and computational analyses revealed crucial features that are distinctively present in pcStar, including the presence of an extra solvent molecule, high conformational stability and enhanced interactions of the chromophore with its surroundings, tighter tertiary-structure packing and dynamic central-helical deformation. Resulting from the triple mutations, all of these structural features are likely to establish a mechanistic link to the greatly improved fluorescent performance of pcStar. The data described here not only provide a good example illustrating how distant amino-acid substitutions can affect the structure and bioactivity of a protein, but also give rise to strategic considerations for the future engineering of more widely applicable PCFPs.

Background: Insecticide resistance poses a significant challenge in the implementation of vector-borne disease control strategies. We have assessed the resistance levels of Aedes albopictus to deltamethrin and pyriproxyfen (PPF) in Fujian Province (China) and investigated the correlation between these resistance levels and mutations in the voltage-gated sodium channel (VGSC). Methods: The WHO bioassay protocol was used to evaluate the resistance coefficient of Ae. albopictus to deltamethrin and PPF, comparing a susceptible population from the Foshan (FS) area with wild populations from the Sanming (SM), Quanzhou (QZ), Zhangzhou (ZZ), Putian (PT) and Fuzhou (FZ) areas in Fujian Province. Genomic DNA was analyzed by PCR and sequencing to detect knockdown resistance (kdr) in the VGSC, specifically at the pyrethroid resistance alleles V1016V, I1532I and F1534F. Molecular docking was also performed to analyze the binding interactions of PPF and its metabolite 4'-OH-PPF to cytochrome P450 (CYP) 2C19, 2C9 and 3A4 and Ae. albopictus methoprene-tolerant receptors (AeMet), respectively. Results: The analysis of resistance to deltamethrin and PPF among Ae. albopictus populations from the various regions revealed that except for the sensitive population in FS and the SM population, the remaining four regional populations demonstrated resistance levels ranging from 4.31- to 18.87-fold for deltamethrin and from 2.85– to 3.62-fold for PPF. Specifically, the FZ and PT populations exhibited high resistance to deltamethrin, whereas the ZZ and QZ populations approached moderate resistance levels. Also, the resistance of the FZ, PT and ZZ populations to PPF increased slowly but consistently with the increasing trend of deltamethrin resistance. Genomic analysis identified multiple non-synonymous mutations within the VGSC gene; the F1534S and F1534L mutations showed significant resistance to deltamethrin in Ae. albopictus. Molecular docking results revealed that PPF and its metabolite 4'-OH-PPF bind to the Ae. albopictus AeMet receptor and CYP2C19. Conclusions: The wild Ae. albopictus populations of Fujian Province showed varying degrees of resistance to deltamethrin and PPF and a trend of cross-resistance to deltamethrin and PPF. Increased vigilance is needed for potential higher levels of cross-resistance, especially in the PT and FZ regions. Graphical

Background: Steroid 5-Alpha-reductase type I (SRD5A1) converts testosterone to dihydrotestosterone and regulates sex hormone levels, which facilitates tumor incidence or progression. However, the molecular mechanism behind SRD5A1's role in pan-cancer remains unknown. Methods: RNA-seq data from TCGA and the Genotype-Tissue Expression (GTEx) database were used to examine SRD5A1 expression. String, HPA, GEPIA2, TIMER2, and cBioportal database were used to explore the protein and immune cell infiltration information of SRD5A1. The R package “ClusterProfiler” was used to conduct KEGG and GO enrichment analyses, and CancerSEA was used to investigate the functional heterogeneity of cancer cells. Results:SRD5A1 expression was differentially and higher predicted worse survival status in most tumor samples. Increased expression of SRD5A1 was detrimental to the clinical prognoses of cancer patients, especially UCEC. SRD5A1 expression was closely correlated with T cell infiltration and immune checkpoints. There were significant correlations between SRD5A1 expression and tumor mutation burden (TMB) or microsatellite instability (MSI)in several cancers. High SRD5A1 levels were associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 subsets of CD4+ T cells in most cancers. Enrichment analyses revealed that SRD5A1 participated in Transcription Androgen Receptor nuclear signaling and Metabolism. Finally, we validated pan-cancer SRD5A1 expression, and its impacts on immune infiltrate in UCEC.Conclusion:Our results suggest that SRD5A1 may contribute to the immune infiltration in the tumor microenvironment. SRD5A1 might synergize with other immune checkpoints serve as a carcinogenic indicator related to prognosis in pan-cancer, especially UCEC, and shed new light on therapeutics of cancers for clinicians.