The emergence of superbugs with both high pathogenicity and high antimicrobial resistance poses a major challenge to public health. In Staphylococcus aureus, α-hemolysin (Hla) is a key virulence factor mediating infection and thus represents a crucial target for prevention and control. This review first summarized the structural characteristics of Hla in its monomeric crystalline form and heptameric pore assembly. It then systematically delineated the multi-layered and fine-tuned regulation of Hla expression, involving the hla gene locus, the Agr quorum-sensing system, the Sar protein family, the Staphylococcal accessory element regulator (SaeRS) two-component system, and other auxiliary regulators. The pathogenic mechanisms of Hla were further elaborated from the perspectives of both cellular effects and host receptors. Finally, this review summarized recent advances in prevention and treatment strategies targeting Hla, including vaccines, monoclonal antibodies, natural compounds, and nanoparticles, offering new insights and candidate approaches for the precise prevention of drug-resistant S. aureus infections.

The health risks posed by pathogenic microbial contamination in drinking water are becoming increasingly apparent. Following exposure to pathogens via water, the human body may experience reactions ranging from infection and illness to death. However, the current Standards for Drinking Water Quality (GB 5749—2022) primarily rely on indicator microorganisms to evaluate water quality, lacking precise targets for pathogen control and load levels, which makes it difficult to accurately assess the actual hazards posed by microorganisms in drinking water. Therefore, clarifying the relationship between the intake dose of pathogenic microorganisms in drinking water and the risk of human infection is of great significance for safeguarding public health. Quantitative microbial risk assessment (QMRA) can be employed to evaluate the health risks posed by pathogenic microorganisms in drinking water. It is currently combined with high-throughput molecular technologies such as real-time quantitative PCR, digital quantitative PCR, metagenomics, and metaviromics, overcoming the limitations of conventional culture-based methods in identifying pathogenic hazards and demonstrating significant advantages in pathogen hazard identification and multidimensional traceability. This paper reviews the research progress in the quantitative monitoring and risk assessment of pathogenic microorganisms in drinking water. On the basis of the distribution patterns and quantitative detection of pathogenic microorganisms, QMRA is employed to conduct risk prediction, screen high-risk pathogens, and identify critical control points, and thus a systematic approach for precise prevention and control and full-chain governance is ultimately established. This approach integrates multi-omics technologies, big data analysis, and health impact assessment, achieving a transition in water quality safety management from reactive response to proactive prevention and providing robust scientific support for ensuring drinking water safety and the health of vulnerable populations.

Driven by the continuous pressure of antibiotic selection, bacteria continue to evolve through multidrug resistance mechanisms, resulting in the increasing ineffectiveness of conventional antibiotic treatment and posing a severe challenge of no drug availability in clinical practice. Nano-delivery systems breathe new life into antimicrobial therapy with their designable physicochemical properties and versatile integration characteristics. Nano-delivery systems are not limited to simple drug carriers, but can be developed into a multi-functional intelligent platform integrating precise delivery, microenvironment perception, and immune reprogramming through precision design. This review systematically expounds the construction strategy of antimicrobial nano-delivery systems, sorts out the development context from drug carrier, synergistic vector, intelligent response vector to intelligent biomimetic vector. Furthermore, this review discusses the targeted design and antimicrobial component loading strategy in detail, including conventional antibiotic synergy and new antimicrobial co-delivery. The core thesis of this paper is that the application of nano-delivery systems in specific infection scenarios (e.g., intracellular bacterial infection and biofilm-associated infection) has gone far beyond simple delivery, and instead actively regulates host immune homeostasis, synergistically enhancing antibacterial effects by regulating innate immunity (e.g., macrophage polarization and neutrophil function) and activating adaptive immunity. Finally, this paper makes an outlook on the challenges and future development directions of this field, emphasizing that through cross-scale design and multi-mechanism synergy, nano-delivery systems are expected to provide a new generation of therapeutic strategies that are efficient, safe, and less likely to induce drug resistance for drug-resistant bacterial infections.

Lipid metabolism disorders have emerged as a global health challenge, and gut microbiota dysbiosis, along with the consequent metabolic endotoxemia, are key factors promoting this pathological process. This review summarizes the molecular mechanisms by which natural active components (NACs) improve lipid homeostasis through targeted modulation of gut microecology. At the microecological intervention level, NACs optimize the microbiota structure by increasing the abundance of functional bacteria such as Bifidobacterium and Akkermansia muciniphila, while inhibiting the proliferation of opportunistic pathogens like Desulfovibrio. At the “metabolite-host” interaction level, the lipid-lowering mechanisms mainly involve two aspects. The first is the targeted effects of metabolites, wherein short-chain fatty acids, secondary bile acids, and phenolic acid derivatives specifically modulate metabolic targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid synthase. The second is the host signaling responses, wherein the aforementioned metabolic mediators synergistically modulate key signaling nodes, such as adenosine 5′-monophosphate-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptors (PPARs), to inhibit de novo lipogenesis and promote fatty acid β-oxidation, while simultaneously inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway to alleviate inflammation-associated abnormal lipid deposition. The “component-microbiota-metabolite-host signaling” regulatory mechanism outlined herein provides a theoretical reference for elucidating the pharmacodynamic material basis of NACs and developing gut microecology-based personalized nutritional intervention strategies.