Changchun University of Chinese Medicine

We studied the viromes of three dominant mosquito species in Wenzhou, a coastal city in Zhejiang Province, using metavirome sequencing, with 18 viral families identified. Viral sequences were verified by RT-PCR. The JEV E gene was most closely related to the 1988 Korean strain. DENV sequences were most closely related to the 1997 Australian strain. CHIKV-E1-1 was most closely related to the 1983 Senegal strain and belonged to West African genotype CHIKV. Remarkably, this is the first time that a West African genotype of CHIKV has been detected in Zhejiang Province. Mutations in the CHIKV-E1-1 protein A226V may increase infectivity in Ae. albopictus. Three non-conservative mutations of CHIKV-E1-1 (D45H, D70H and V290D) may have an impact on the function. In conclusion, our study reveals the diversity of mosquito-borne viruses and potential emerging outbreaks in the southeast coastal region of China, providing new perspectives for mining the ecological characterization of other important arboviruses.

Staphylococcus aureus (S. aureus) is a prevalent pathogen responsible for a wide range of diseases in humans, contributing to both hospital-acquired and community-acquired infections.The von Willebrand factor-binding protein (vWbp) is pivotal for S. aureus pathogenicity because it induces blood coagulation, thereby facilitating bacterial survival and dissemination within the host.Notably, the absence of vWbp does not hinder S. aureus growth, indicating that vWbp is an attractive target for combating S. aureus infections while mitigating the risk of antibiotic resistance.Our findings revealed that tanshinone I significantly inhibited vWbp-induced coagulation without affecting the proliferation of S. aureus.Hemolysis assays confirmed the biocompatibility of tanshinone I, while Western blot anal., fluorescence quenching, and thermal shift assays (TSAs) demonstrated that tanshinone I does not alter vWbp expression but directly binds to the protein.Mol. docking studies elucidated the interaction mechanism, identifying ARG-479 and GLN-484 as critical residues for tanshinone I binding.Furthermore, in vivo studies demonstrated that tanshinone I reduces lung tissue damage in mice infected with S. aureus, thereby increasing survival rates.Addnl., tanshinone I was tested in greater wax moth larvae and showed similar protective effects.In conclusion, tanshinone I effectively inhibits vWbp, reducing the virulence of S. aureus.This study underscores the potential of tanshinone I as a therapeutic agent against S. aureus infections, offering a novel strategy to combat bacterial infections while decreasing the critical issue of antibiotic resistance.

The 2022 monkeypox outbreak involved rapid global dissemination, prompting research into animal models for the monkeypox virus (MPXV), including non-human primates and mice. However, studies utilizing rabbits as models remain limited. In this study, we established three rabbit models using the current epidemic MPXV strain. Following intravenous MPXV injection, adult rabbits exhibited characteristic clinical manifestations, including widespread rash and fever, with viral replication in the skin, lungs, and testes, resulting in severe pathological damage by 6 days post-infection (dpi). Intradermal injection of MPXV into the dorsal skin of adult rabbits produced red lesions with central necrosis and hemorrhage accompanied by dense inflammatory infiltrates. Abundant viral particles were observed in epidermal cells at 6 dpi. Additionally, a fatal MPXV model was developed in 10-day-old rabbits using intranasal virus administration. These young rabbits exhibited lethargy and diarrhea beginning at 2 dpi, significant weight loss, and a 50% mortality rate by 15 dpi. Viral dissemination was detected in multiple organs, leading to extensive multi-organ damage. This study highlights the utility of rabbit models for MPXV, displaying typical clinical features and pathogenic mechanisms.