Pitching cGAMP as a vaccine strategy: One strategy to address the variable effectiveness of many influenza vaccines is to induce antiviral resident memory T cells, which can mediate cross-protection against multiple substrains (heterosubtypic immunity). Unfortunately, such vaccines typically use attenuated active viruses, which may be unsafe for certain populations. Wang et al. report a vaccine using an inactivated virus that effectively induced heterosubtypic immunity in both mice and ferrets (see the Perspective by Herold and Sander). They coadministered the virus with 2′,3′-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), a potent activator of the innate immune system, encapsulated in pulmonary surfactant–biomimetic liposomes. This adjuvant was taken up by alveolar epithelial cells, whose activation resulted in effective antiviral T cell and humoral immune responses without accompanying immunopathology. Science , this issue p. eaau0810 ; see also p. 852

Development of alternatives to antibiotics is one of the top priorities in the battle against multidrug-resistant (MDR) bacterial infections. Here, we report that two naturally occurring nonantibiotic modalities, blue light and phytochemical carvacrol, synergistically kill an array of bacteria including their planktonic forms, mature biofilms, and persisters, irrespective of their antibiotic susceptibility. Combination but not single treatment completely or substantially cured acute and established biofilm-associated Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus infections of full thickness murine third-degree burn wounds and rescued mice from lethal Pseudomonas aeruginosa skin wound infections. The combined therapy diminished bacterial colony-forming units as high as 7.5 log₁₀ within 30 min and introduced few adverse events in the survival of cocultured mammalian cells, wound healing, or host DNA. Mechanistic studies revealed that carvacrol was photocatalytically oxidized into a series of photoreactive substrates that underwent photolysis or additional photosensitization reactions in response to the same blue light, forming two autoxidation cycles that interacted with each other resulting in robust generation of cytotoxic reactive oxygen species. This phototoxic reaction took place exclusively in bacteria, initiated by blue light excitation of endogenous porphyrin-like molecules abundantly produced in bacteria compared with mammalian cells. Moreover, no bacterial resistance developed to the combined treatment after 20 successive passages. This highly selective phototoxic reaction confers a unique strategy to combat the growing threat of MDR bacteria.

Bacterial or fungal membrane vesicles, traditionally considered as microbial metabolic wastes, are secreted mainly from the outer membrane or cell membrane of microorganisms. However, recent studies have shown that these vesicles play essential roles in direct or indirect communications among microorganisms and between microorganisms and hosts. This review aims to provide an updated understanding of the physiological functions and emerging applications of bacterial membrane vesicles, with a focus on their biogenesis, mechanisms of adsorption and invasion into host cells, immune stimulatory effects, and roles in the much‐concerned problem of bacterial resistance. Additionally, the potential applications of these vesicles as biomarkers, vaccine candidates, and drug delivery platforms are discussed.

Phototherapy can offer a safe and non-invasive solution against infections, while promoting wound healing. Conventional phototherapeutic devices are bulky and limited to hospital use. To overcome these challenges, we developed a wearable, flexible red and blue LED (r&bLED) patch controlled by a mobile-connected system, enabling safe self-application at home. The patch exhibits excellent skin compatibility, flexibility, and comfort, with high safety under system supervision. Additionally, we synthesized a sprayable fibrin gel (F-gel) containing blue light-sensitive thymoquinone and red light-synergistic NADH. Combined with bLED, thymoquinone eradicated microbes and biofilms within minutes, regardless of antibiotic resistance. Furthermore, NADH and rLED synergistically improved macrophage and endothelial cell mitochondrial function, promoting wound healing, reducing inflammation, and enhancing angiogenesis, as validated in infected diabetic wounds in mice and minipigs. This innovative technology holds great promise for revolutionizing at-home phototherapy for chronic infected wounds.

Since their discovery, Black Phosphorus (BP)-based nanomaterials have received extensive attentions in the fields of electromechanics, optics and biomedicine, due to their remarkable properties and excellent biocompatibility. The most essential feature of BP is that it is composed of a single phosphorus element, which has a high degree of homology with the inorganic components of natural bone, therefore it has a full advantage in the treatment of bone defects. This review will first introduce the source, physicochemical properties, and degradation products of BP, then introduce the remodeling process of bone, and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels, polymer membranes, microspheres, and three-dimensional (3D) printed scaffolds. Finally, we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application.