Enzymatic biosynthesis has become increasingly crucial in green chemistry and biosynthesis. However, current computational tools struggle to effectively integrate enzyme identification with pathway synthesis due to the specificity of enzymes and their complex interactions with substrates. Here, we propose EnzRetro, a novel framework for enzymatic retrosynthesis that provides an end-to-end solution bridging retrosynthesis planning with enzymatic engineering. The core innovative concept of EnzRetro is site-specific reaction edits (SSREdits), a dynamic approach to representing structural transformations at specific enzyme active sites and forging a direct link between enzyme identification and reaction patterns. To enable the model to learn meaningful representations of SSREdits, we developed three pretraining tasks and then fine-tuned two specialized models: (1) the SSREdits generation model for pathway synthesis, which translates the target product into a sequence of reaction edits, and (2) the EC generation model for enzyme identification, which focuses on precise transformation sites within SSREdits, enabling generalization across diverse reactions. Extensive experiments demonstrate the superior performance of EnzRetro, with a promising 56.1% and 97.7% Top-1 accuracy on USPTO-50k dataset for retrosynthesis and ECREACT dataset for enzyme identification, respectively. Finally, EnzRetro combines the two-stage processes of retrosynthesis and enzyme identification into one-pot learning, enhancing both computational efficiency and interpretability, and bridging the gap between pathway synthesis and enzyme identification. The accuracy of EnzRetro has been validated by three enzymatic pathways. We developed a web platform for multi-step retrosynthesis planning that reconstructs multiple enzymatic pathways for putrescine biosynthesis with substantial diversity and significantly outperforms state-of-the-art baselines.

Basalt fiber fabric (BFF) has gained extensive application in industrial, military, and aerospace fields due to its lightweight nature, chemical inertness, and mechanical durability. However, the inherent surface inertness and electrical insulation of BFs restrict their utilization in electromagnetic interference (EMI) shielding. In this work, we propose an innovative gradient functionalization strategy based on “plasma activation-ALD bridging-chemical plating-post annealing treatments” to fabricate polychromatic BFs with exceptional EMI and thermal shielding performance. Plasma pretreatment synergizes with ALD TiO₂ to enrich hydroxyl groups, serving as atomic-scale “bridges” for anchoring dense Ni coatings. This process establishes interconnected conductive networks to reflect EM waves, while post annealing induces interfacial reconstruction, enhancing EMI shielding effectiveness (SE) through synergistic magnetic loss and interfacial polarization mechanisms. The optimized BFF demonstrates an outstanding EMI SE of 53.47 dB and maintains stable performance under high-temperature and cryogenic conditions. Additionally, vivid and uniform structural colors derived from thin-film interference were achieved on the fiber surface by modulating annealing temperatures. Notably, the high refractive index characteristics of TiO₂, Ni, and NiO layers, coupled with their multiple refractive synergistic effects, lead to pronounced interfacial reflection of infrared radiation, which effectively reduces the radiation flux penetrating BFFs and significantly enhances overall shielding performance, underscoring their potential in thermal camouflage applications. This study establishes a groundbreaking strategy for designing multi-color BFFs with EM and thermal shielding capabilities, and provides novel insights for developing multifunctional shielding materials while expanding BFF's application horizons in chromatic engineering and radiation protection domains.

Reliable in vitro liver models are indispensable for researching liver diseases and developing medications. Present 2D/3D cell cultures and animal models inadequately replicate the intricacy of living systems and in vivo conditions, resulting in impaired cellular functions. They also fail to emulate tissue-like architectures, which undermines their precision. Meanwhile, animal models present species differences, making real-time observation of dynamic results inconvenient and raising serious ethical concerns. Therefore, there is an urgent need to develop alternative tissue models with biomimetic human pathophysiology to bridge the gap between clinical trials and traditional human and animal models. Liver-on-a-chip (LOC) technology, based on microfluidics, is an innovative in vitro modeling device that can replicate the microstructures and tissue-tissue interfaces of specific liver functional units, simulating organ and tissue-level physiological activities. This review summarizes recent strategies and breakthroughs in LOC technologies, from biomimetic tissues and extracellular matrix construction in liver microphysiological systems to diverse LOC development approaches. Furthermore, we highlight key advances in functional LOC platforms, including 3D bioprinting, vascularization strategies, and the incorporation of liver buds and organoids to enhance physiological relevance. The integration of deep learning and sensor technologies for intelligent, real-time monitoring is also discussed. Finally, we examine LOC applications in drug screening and disease modeling, assess challenges in clinical translation, and offer perspectives on future directions in biomedical research and personalized medicine.

Subacute rumen acidosis (SARA) is a critical metabolic disorder in dairy ruminants that threatens their milk production. However, the mechanisms by which rumen fungi influence the susceptibility and tolerance of ruminants to SARA remain unclear. This study investigated the relationship between rumen fungal metabolic functions and host SARA tolerance by examining the rumen epithelial miRNA-mRNA correlations and further cell subtype variations affected by fungi. SARA-susceptible and SARA-tolerant goats were identified by monitoring the dynamic rumen pH during high-concentrate feeding. The abundance of anaerobic fungi and their cellulose and amino acid metabolic functions were reduced in SARA-susceptible goats, but the enrichment of Aspergillus bombycis, which is associated with increased thiamine metabolism, offers potential for SARA tolerance. Furthermore, this study revealed that Aspergillus bombycis negatively regulates the rumen epithelial chi-miR-17-26080 through enhanced thiamine metabolism, thereby reducing its inhibitory effect on insulin-like growth factor binding protein 2 (IGFBP2). The tolerance mechanism of SARA was further explored by adding thiamine to high concentrations, which revealed that the upregulation of IGFBP2 promoted rumen epithelial IGF1 recruitment and increased the content of IGF1, which activated the ERK and PI3K/AKT pathways, further increasing the expression of CDK4 and Cyclin A2 and promoting the rumen epithelial cells' proliferation. The increased number of rumen spinous and basal cells in SARA-tolerant goats enhances volatile fatty acids absorption in dairy goats, leading to improved SARA tolerance. These findings highlight the roles of rumen fungi and their produced thiamine in preventing SARA in ruminants by enhancing epithelial cell proliferation via the IGFBP2/IGF1 axis activation.

²²³Ra, a potent α-emitting radionuclide, is currently limited to treating bone metastases in clinical practice. This constraint stems from the lack of stable chelating agents capable of withstanding its high recoil energy and the five decay daughters produced during decay, hindering its application in targeted α-therapy (TAT). Ultrasmall gold nanoclusters (AuNCs) exhibit favorable pharmacokinetics, featuring tunable blood half-life, renal clearance, and low hepatic/splenic sequestration. Given gold's high atomic number and structural flexibility, we hypothesized that AuNCs could encapsulate ²²³Ra and its decay progeny, serving as an effective carrier for tumor TAT. Density functional theory simulations revealed that Au_10–12 nanoclusters, particularly a catenane-structured Au₁₀, could incorporate ²²³Ra and its daughters with favorable energy dynamics. We then engineered α_vβ₃-targeted AuNCs co-labeled with ²²³Ra and ⁶⁸Ga (⁶⁸Ga/²²³Ra@AuNCs-RGD). Molecular docking confirmed receptor specificity, while in vitro and in vivo studies demonstrated tumor-specific targeting. PBPK modeling and Monte–Carlo simulations showed prolonged circulation (t_1/2β = 139.4 min), renal clearance, sustained tumor retention, and efficient tumor energy deposition. The ⁶⁸Ga/²²³Ra@AuNCs-RGD platform achieved complete tumor regression and stimulated antitumor immunity, suggesting potential for TAT–immunotherapy synergy. This study establishes a theoretical foundation for stably doping ²²³Ra into gold clusters and provides a framework for developing novel ²²³Ra-based α-radiopharmaceuticals with significant clinical translation potential.

Alzheimer's disease (AD) pathogenesis is strongly influenced by APOE4, though how cooperative genetic factors modulate this relationship remains unclear. While genomic studies have tentatively linked RBFOX1 to AD susceptibility, its functional synergy with APOE4 has never been experimentally defined. We engineered APOE3 or APOE4 isogenic human cerebral organoids with CRISPR/Cas9-mediated RBFOX1 knockout. Remarkably, RBFOX1 depletion selectively triggered robust microglial generation exclusively in APOE4 organoids. Time-course gene expression revealed that this APOE4-specific effect correlated with prolonged mesodermal priming during early embryoid body differentiation, creating a permissive niche for microglial lineage specification. The emergent microglia exhibited pronounced neurotoxic phenotypes, including pro-inflammatory factor secretion, synaptic architecture remodeling, and lipid droplet accumulation in organoids. These changes coincided with aggravated Tau hyperphosphorylation and electrophysiological abnormalities, collectively mirroring multifaceted AD pathology. Our findings establish RBFOX1 as a potential AD protective factor, a critical suppressor of APOE4-glia crosstalk, and demonstrate that its loss unleashes a microglia-mediated neurodegenerative cascade. By developing cerebral organoids with autonomous microglial networks, we present a platform capable of modeling genotype-dependent neuron-glia interactions in AD, opening new avenues for mechanistic and therapeutic exploration.

Effectively delivering therapeutics to deep tumor regions is crucial for successful treatment but remains a formidable challenge. The severe hypoxia common in these areas can inhibit various therapeutic-induced cell death pathways, including ferroptosis. Herein, we present the design of a bacterial biohybrid (Ec@ZFOY) with dual magnetic and hypoxic tropism for targeted therapeutic delivery and ferroptosis activation in the deep tumor region. This biohybrid is constructed using hypoxia-targeted Escherichia coli and magnetic Zn_0.16Fe_1.24O₄ (ZFO) nanoparticles loaded with YC-1, a hypoxia-inducible factor-1α (HIF-1α) inhibitor. ZFO exhibits peroxidase- and glutathione oxidase-mimetic activities, catalyzing tumor-derived H₂O₂ into hydroxyl radical and inhibiting glutathione peroxidase 4, thereby inducing ferroptosis. Additionally, Ec@ZFOY demonstrates pH-responsive YC-1 release, which inhibits HIF-1α and reduces lipid droplets, enhancing ferroptosis through the release of polyunsaturated fatty acids. Both in vitro and in vivo experiments confirm the significant therapeutic efficacy of Ec@ZFOY. This study unveils the design of magnetically and hypoxia-tropic bacterial biohybrids for activating ferroptosis in deep tumor sites, highlighting their potential for other therapeutic delivery and disease modulation applications.

Prostate cancer (PCa) is the most frequently diagnosed cancer in males. Advanced PCa is invasive and may spread rapidly. Current strategies could not fulfill the requirement for clinical application; thus, novel therapeutic strategies are still urgently needed. Nanoparticles are a promising strategy for targeted drug delivery and cancer treatment; however, the strong exogeneity and weak targeting limit their further application. Here, we developed a novel macrophage membrane-coated nanoparticle that has transmembrane-expressed gy-1, a single-chain antibody fragment (scFv) against prostate-specific membrane antigen (PSMA), to endow the immune evasion and targeting property, which we named P-MMCNPs. The Fe₃O₄@Au nanoparticles were used as the core of P-MMCNPs, which confer P-MMCNPs with the properties of multimodal imaging and photothermal therapy (PTT). Anti-tumor cytotoxic drug maytansine (DM1) was loaded into the nanoparticles to obtain cytotoxicity. P-MMCNPs were shown to have immune evasion capacity and prolonged circulation time and can be specifically distributed in PSMA-positive tumors, thus enabling targeted imaging and targeted drug delivery. The macrophage membrane-coated nanoparticles combined to inhibit tumor growth in vivo when loaded with DM1 and treated with PTT. Additionally, we found that P-MMCNPs alone could inhibit tumor growth, which may be caused by cytokine neutralization by the macrophage membrane. Our work demonstrates that the innovative P-MMCNPs serve as a versatile platform. This platform improves PCa-targeted diagnostic and therapeutic efficacy while avoiding side effects. Moreover, it holds promise for expanding into the diagnosis and treatment of other diseases, with potential for clinical translation. Additionally, it offers novel insights into nanomedicine-based combination therapy.

The heart, as the central organ of the circulatory system, undergoes distinct metabolic transitions from embryonic development through postnatal maturation. A key aspect of this transition is mitochondrial maturation, which is influenced by changes in oxygen levels and metabolic substrates. These changes regulate cardiac structure and function by affecting signaling pathways and transcription factors. In cardiovascular diseases, mitochondria play a crucial role in altering metabolic patterns, contributing to pathological remodeling and worsening disease outcomes. This article explores mitochondrial roles in both cardiac development and disease progression, offering insights into potential therapeutic interventions.

Flexible electrochromic displays (ECDs) demonstrate low energy consumption, good readability, and high color contrast. However, their performance deteriorates in dark environments due to the reliance on environment light. Herein, we propose a flexible multi-mode electrochromic display (FMECD), which is designed to effectively integrate electrochromism-photoluminescence-mechanoluminescence (EC-PL-ML) functionalities. The PL and ML serve as backlight to simulate a natural light condition for display in dark environment. The function is realized by incorporating tannic-acid-modified polydimethylsiloxane (PDMS), incorporated with ZnS: Cu phosphor as a backlight, onto which patterned tungsten trioxide (WO₃)-EC devices are applied. The FMECD shows a large optical modulation of 75.8% and maintains robust EC performance with a reflection retention of 86% after 200 stretching cycles, and 91.5% after 500 bending cycles. Notably, compared to commercial organic light-emitting diode (OLED) displays, the FMECD significantly reduces energy consumption from 172.2 Wh m^-2 to 0.0075 Wh m^-2. As a proof of concept, we demonstrate the functionality of the FMECD as a patterned display that visualizes various motion states of different body parts in multiple scenarios of dark environments, advancing the development of wearable intelligent displays for human motion monitoring and signal patterning.

Affected by the complexity and heterogeneity of the tumor redox microenvironment, chemotherapy often fails to achieve satisfactory clinical outcomes. Modular design of prodrug nanoassemblies presents tremendous potential in upgrading the therapeutic index of chemotherapeutic agents. Given the biochemical vulnerability of tumor redox homeostasis, we fabricated five-membered cyclic chalcogenide-linked paclitaxel prodrug nanoassemblies, which realized tumor site-specific activation and reshaped the pro-apoptotic tumor redox homeostasis. Cyclic diselenide and cyclic disulfide bonds integrated the modification modules and response modules to minimize the utilization of non-pharmacodynamic moieties and increase druggability. Importantly, the modification-response integrated modules could simultaneously block the glutathione-glutathione peroxidase (GSH/GPx) antioxidant system and amplify reactive oxygen species (ROS) generation. The reshaping of the tumor redox homeostasis cascade triggered the loss of mitochondrial membrane potential and apoptosis of tumor cells, which synergistically potentiated the antitumor effects of paclitaxel. Such an intelligent prodrug nanoplatform brought new perspectives for constructing advanced antitumor nanomedicines with significant clinical research value.

Accurate nucleic acid-based pathogen diagnosis is critical for clinical treatment and epidemic control. However, present gold-standard testing methods based on nucleic acid amplification are limited by their time and labor-intensive nature. Hence, we reported an amplification-free assay that facilitates rapid, sensitive, and point-of-care detection of infectious diseases. Herein, spherical nucleic acid (SNA)-stabilized cage-type three-dimensional electrochemiluminescence (ECL) reporter probe, constructed utilizing Ru(dcbpy)₃Cl₂-doped NH₂-MIL-101 (Fe) metal-organic framework, was combined with a paper-based bipolar electrode ECL sensor. Furthermore, surface modifications were performed using polydopamine and SNAs to further improve the stability. Notably, compared with the ordinary Ru(dcbpy)₃Cl₂, the modified ECL probe attained 10³-fold enhancement in luminous efficiency. The developed ECL-based nucleic acid biosensing system offers the advantages of simplicity, portability, low cost, and user-friendly nucleic acid detection, with a sample-to-answer time of approximately 15 min. Additionally, the effectiveness of the developed assay in detecting pathogenic nucleic acid was assessed using Mpox and SARS-Cov-2, exhibiting a wide dynamic range from 33 to 10¹⁰ aM and limits of detection as low as 3 copies/μL. Furthermore, the assay exhibited 100% sensitivity and specificity when validated against quantitative polymerase chain reaction-based detection using clinical samples. Altogether, the findings of this study show the efficacy of the novel developed SNA-stabilized cage-type 3D ECL probe-enhanced nucleic acid assay, along with its potential as a promising paradigm for point-of-care diagnosis of infectious pathogens.

Three-dimensional (3D) multicellular models are considered ideal methods for bridging the gap between two-dimensional (2D) cell culture and animal models, which are widely used in organogenesis, disease models, drug development, and regenerative medicine. Cell culture technologies determine the physical and biological properties of multicellular spheroids or organoids that affect the authenticity, stability, assessment, and throughput of the 3D multicellular system. Micro patterns, characterized as a coating of specific adhesion matrices on substrates, can control cell behaviors and fate by limiting the space available for cell spreading. micro patterns are used to culture non-tumor or tumor spheroids and organoids with effective control of size and arrangement, which is suitable for large-scale and standardized culture to generate 3D multicellular models. This comprehensive review summarizes the advantages and applications of 3D multicellular models and discusses the characteristics of general 3D cell culture technologies. We discuss the basic applications of micro pattern technologies and highlight the specific advantages and features of micropattern (as a 3D cell culture platform) in non-tumor research (regenerative medicine, developmental biology, disease modelling, and monoclonal cell culture) and tumor research (tumor microenvironment (TME) and drug screening). Finally, the fabrication of micro patterns (bio inks, fabrication methods for micro patterns, morphology, and quality of micro patterns) is described.

As the global energy crisis intensifies and environmental pollution continues to deteriorate, harnessing solar energy through photocatalytic processes is emerging as a leading strategy to meet energy needs and combat climate crisis. Natural photosynthesis, the oldest and most fundamental photocatalytic system, converts sunlight, water, and CO₂ into useful chemicals that sustain all forms of life. Inspired by this process, a range of artificial photosynthesis systems have been developed to store solar energy in chemical bonds. Conjugated microporous polymers (CMPs) have gained increasing attention as innovative photocatalysts, owing to their unique properties such as tunable light-harvesting abilities, robust porous architectures, and extended π-conjugated frameworks. This review outlines recent progress in the application of CMPs as photocatalysts, offering a comprehensive and critical analysis. It begins by introducing the evolution, preparation methods, and catalytic mechanisms of CMPs. The application of CMP-based photocatalysis in hydrogen evolution, CO₂ conversion, biomass valorization, and degradation of harmful substances are then described. Finally, future perspectives of CMPs as photocatalysts are presented, highlighting the key challenges and opportunities in their adaptation for solar energy conversion.

The extracellular matrix (ECM) is vital for tissue regeneration and remodeling by providing structural support and regulating cell behavior. Bioactive membranes derived from decellularized ECM show promising regenerative potential in many fields. However, they still face challenges such as immune rejection, structural disparities, and high costs associated with human-derived materials. These issues hinder their widespread clinical application and limit their adaptability to personalized treatments. Further research is needed to improve the safety, efficacy, and accessibility of ECM-based materials. This study develops an autologous ECM-based membrane, termed adipose-derived matrix film (ADF), using a simple physical method inspired by traditional “papermaking.” ADF exhibits favorable biological activity and mechanical strength, essential for tissue regeneration. Its production is efficient, facilitating clinical translation. Additionally, ADF can be stored long-term at low temperatures, enabling the establishment of an “ECM bank” for personalized medicine. As a cell-free therapy, ADF enhances soft tissue regeneration and wound healing, with Trem2⁺ macrophages playing a key role in neovascularization. We introduce a novel autologous adipose ECM-derived bio-membrane, offering new perspectives on ECM preservation and Trem2⁺ macrophage-mediated regeneration. These findings significantly advance cell-free regenerative medicine and redefine fundamental mechanisms of tissue repair and vascular restoration.

Recalcitrant airway inflammatory diseases have drawn significant attention due to their high incidence and substantial healthcare costs. Analysis of clinical samples from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) revealed the coexistence of neutrophilic and eosinophilic inflammation, which may account for the limited efficacy of traditional single-target therapeutic strategies. Moreover, cell-free DNA (cfDNA)—an emerging inflammatory mediator—has been implicated in both eosinophilic and neutrophilic responses through its role in the formation of extracellular traps. In this study, we developed tannic acid (TA)-modified CuInP₂S₆ (CIPS) nanosheets (C-TA₁; w/w = 1:1) as a multi-targeting therapeutic nanoplatform for recalcitrant airway inflammatory diseases. The C-TA₁ nanosheets demonstrated efficient cfDNA clearance via hydrogen bonding interactions, thereby inhibiting cfDNA-triggered toll-like receptor 9 (TLR9) activation and subsequent nuclear factor-κB (NF-κB) inflammatory signaling. Additionally, C-TA₁ exhibited potent antioxidant and antibacterial activities, which were ascribed to the inherent properties of the two-dimensional nanostructure and the chemical characteristics of TA, respectively. The in vivo therapeutic efficacy of C-TA₁ was evaluated in murine models with neutrophilic and eosinophilic airway inflammation, respectively. C-TA₁ markedly attenuated airway inflammation in both of these animal models by reducing reactive species, immune cell infiltration, goblet cell hyperplasia and the expression of pro‑inflammatory cytokines. Furthermore, treatment with C-TA₁ effectively modulated the dysregulated airway microbiota observed in the inflammatory state. Our findings demonstrate a multi-targeting nanoformulation designed to mitigate multiple key pathological drivers of severe airway inflammation concurrently. This engineered system presents a promising strategy for managing respiratory inflammatory disorders and also other inflammation-related diseases.

Hepatocellular carcinoma (HCC) remains a critical global health challenge with limited treatment efficacy hindered by therapy resistance and hypoxia-induced immune suppression. Tumor heterogeneity and low immune cell reactivity often lead to tolerance and failure of immunotherapy. Sonodynamic therapy (SDT) has emerged as a promising precision treatment with non-invasive characteristics and localized tumor targeting, offering potential for remodeling the immunosuppressive tumor microenvironment. This study introduces a novel phthalocyanine-metal-organic framework hybrid (Pc@Zr-MOF) designed for SDT and immune regulation in HCC. By enhancing the efficiency of ultrasonic conversion and synergy, Pc@Zr-MOF induces robust tumor cell apoptosis while simultaneously reshaping the immune landscape. Single-cell RNA sequencing reveals its ability to promote M1 macrophage polarization and increase cytotoxic T cell infiltration with tumor-associated macrophages. These effects highlight its dual mechanism of direct tumor eradication and immune microenvironment remodeling. Moreover, Pc@Zr-MOF demonstrates admirable biocompatibility and minimal off-target toxicity, which underscores its clinical translational potential. By synergizing SDT with immune reprogramming, this approach addresses hypoxia-driven resistance and establishes durable anti-tumor immunity. This study aims to change the current situation of advanced HCC treatment characterized by reconfiguration of tumor cell subpopulations and immunosuppression, thereby bringing a new paradigm to the precise treatment of HCC.

Previous optogenetic bioelectronic systems have enabled a highly selective way of modulating neural populations by delivering a certain wavelength of light to engage with exogenously expressed light-sensitive proteins, which lay the foundation of therapeutic interventions of neural circuits. However, real-time biofeedback and strategic modulation are crucial for adjusting customized clinical treatment adjustment. To achieve this purpose, we integrated illumination, temperature, and electromyographic (EMG) sensing elements into the optogenetic bioelectronic system to avoid overexposure caused by localized overheating and to provide functional recovery evaluation during neural regeneration, which guides the in situ adjustment of the intensity, frequency, and duration of illumination parameters controlled by a wireless connected programmable external control board. In this study, both in vitro and in vivo experiments were performed to examine the optical, thermal, and electrical characteristics of our bioelectronic system. On this basis, we demonstrated a series of standardized EMG results to evaluate the recovery condition and modify the illumination parameters of each test rat. Combining temperature monitoring feedback and EMG signaling feedback, our optogenetic bioelectronic system enables strategic optogenetic spinal cord injury (SCI) treatment through real-time illumination modulation to achieve customized spinal cord injury treatment.

Developing simple and convenient strategies to eliminate drug-resistant pathogen-transmission routes efficiently is extremely urgent for hospital healthcare. Candidozyma auris (C. auris) is an emerging nosocomial pathogen with multidrug resistance that easily forms biofilms, aggravating the risk of spreading in public places. Herein, a novel visible light-induced disinfectant spray with a boric-acid-functionalized lipophilic cation, TB, was developed. The boronic acid groups enable simultaneous targeting of polysaccharide-rich cell walls and extracellular polymeric substances within biofilms. TB spray achieved a > 99.9% reduction in C. auris with light and reduced biofilm biomass by approximately 85.2%. TB's polysaccharide targeting, pH-enhanced properties, positive charge, and particle size enable it to effectively bind to C. auris in acidic biofilm microenvironments, boosting photodynamic inactivation, collapsing biofilms, and preventing recurrence. It produces reactive oxygen species through Type I and II pathways, ensuring high efficacy even in hypoxic conditions, making it ideal for disinfecting high-touch surfaces. In a rat model of ventilator-associated pneumonia, TB markedly reduced pulmonary C. auris loads by over 100-fold and significantly attenuated lung injury. Furthermore, the breakdown of polysaccharides enhanced the hydrophobicity of both abiotic and biological surfaces, as well as the increased contact angle, inhibiting biofilm adhesion. Multiomics analysis revealed that TB suppressed C. auris by disrupting genes associated with oxidative stress response, ergosterol biosynthesis, and biofilm maintenance. This visible light-induced disinfectant spray holds great potential to combat outbreaks of high-risk pathogens and could revolutionize disinfection practices in healthcare settings.