Fuyang Normal University

Staphylococcus aureus is a well-known pathogenic bacterium that can produce a variety of virulence factors that cause disease in humans. RpiRB is a regulator of metabolic response, whose regulatory role in the virulence of S. aureus is largely unknown. In this study, we demonstrated that the disruption of rpiRB led to down-regulation of the transcription levels of agr-related virulence factors, and reduced the hemolytic activity of methicillin-resistance S. aureus (MRSA). In addition, we also found that RpiRB was involved in regulating the inflammatory response of the host. A mouse subcutaneous abscess model showed that the pathogenicity of the strain was significantly reduced after the destruction of rpiRB. Interestingly, RpiRB enhanced the pathogenic capacity of S. aureus in an agr-dependent manner, while it was directly inhibited by SarA. This study aims to highlight the role of RpiRB in the regulation of the pathogenicity of S. aureus, so as to provide theoretical references for illustrating the infection mechanism and coping strategies of S. aureus.

Diquat is a widely used bipyridyl herbicide, and central nervous system injury (CNSI) is a major cause of death in acute poisoning; early serum markers and underlying mechanisms remain unclear. We prospectively classified acutely poisoned patients into healthy controls (JKDZ), diquat patients without CNSI (NCNSI), patients who developed CNSI during hospitalization (CNSI1), and patients presenting with CNSI (CNSI2). Early serum underwent transcriptomic, proteomic and metabolomic profiling. Multivariate and differential analyses with KEGG/GO enrichment and O2PLS integration identified key pathways and candidate markers, which were evaluated by violin plots and ROC curves. Mechanistic relevance was tested in zebrafish embryos exposed to diquat (Control, 100, 175 mg/L) by assessing developmental toxicity, locomotor behavior and neuroinflammation-related gene expression. Integrated multi-omics clearly separated the four clinical groups and revealed progressive disruption of glycolysis/gluconeogenesis, central carbon and amino-acid metabolism, serotonergic synapse and ferroptosis pathways with increasing CNSI. Integration pointed to early l-histidine depletion, mitochondrial dysfunction and accumulation of the neurotoxic metabolite methylmalonate. Serum 5-hydroxyindoleacetic acid (5-HIAA), BAG1 and CLIC1 strongly discriminated NCNSI from CNSI1/2 (AUC 0.94-1.00). In zebrafish, diquat caused microphthalmia and other malformations, reduced swimming distance and speed, and robust induction of cxclc1c, ifna6, mmp9 and tnfa. In zebrafish, targeted absolute quantification confirmed a dose-dependent decrease in l-histidine and increases in MMA and 5-HIAA following diquat exposure. Clinical multi-omics combined with zebrafish evidence suggests an association between diquat exposure, histidine depletion, mitochondrial stress and methylmalonate accumulation, accompanied by neuroinflammation and CNSI. Serum 5-HIAA, BAG1 and CLIC1 are promising early-warning biomarkers for CNS complications in diquat poisoning.

Multi-mode/signal visualization of heavy metal ions (HMIs) is of great significance for environmental analysis and food safety, but it is still scarce. Herein, a universal dual-mode sensing strategy was initiated for fast visualization of HMIs. Paper sensors were prepared by the copolymerization of CdTe quantum dots-doped silane coupling agent onto filter papers and then anchoring of metal complexants (viz., chromogenic agents). Binary responsivity of the sensors toward HMIs was designed using complex products of HMIs-complexants as response units, in which colorimetry was realized by the complexation-based color developing while fluorometry was achieved in terms of the fluorescence response mediated by inner filter effect and dynamic quenching. By comparison with single-signal sensing, enhanced sensitivity, improved selectivity and widened working range were experimentally proved in such a combined sensing mode. As concept-to-proofs, in-situ dual-mode fast visualization of HMIs in real water samples such as industrial sewage, river water and tap water was testified using Cu²⁺, Ni²⁺ and Fe²⁺ as models. The limit of detection was as low as 0.02 mg/L (colorimetry of Ni²⁺), and the sensing process was as fast as 0.5 min, and the sensing results were validated by smartphone-based digital image analysis in RGB/gray-scale/Lab modes. Besides, fine consistence among the results of dual-mode visual sensing and those of commercial kits and instrumental technique such as fluorescence quantification and ICP-AES further reinforced the credibility of the strategy proposed herein.