Abstract Significant advancements have been made in the development of therapeutic tumor vaccines for hepatocellular carcinoma (HCC) in the past decade. However, the application of this technique is restricted by the paucity of suitable vaccine adjuvant and vaccine formula that could enhance the anti‐cancer efficiency. Here, we demonstrate that a multifunctional tumor vaccine (MTV) that is coated with tumor membrane antigens and loaded with thalidomide (THA) to promote tumor antigen presenting and T cell activation, leading to the activation of T cells at the cancer site. The in vitro and in vivo experiments revealed that MTV significantly inhibits the progression of three types of liver cancer models: malignant ascites, subcutaneous tumors, and in situ liver cancer. As a result, MTV can enhance T cell immune memory, alleviate T cell exhaustion and reprogram cytokine delivery to induce ferroptosis in tumor cells, thus improving the effectiveness of anti‐PD‐1 immunotherapy. This synergistic approach ensures robust immunotherapeutic effects against multiple types of HCC models. Furthermore, our research highlights THA as a potent vaccine adjuvant that can directly enhance the preventive and therapeutic effects of vaccines, proposing a promising strategy for cancer prevention and immunotherapy.

Abstract Fire‐related smoke inhalation‐induced acute lung injury (SI‐ALI) is a prevalent condition in modern fires, characterized by high mortality and a lack of targeted therapeutic options. Previous research has been hindered by instability in smoke generation and modeling methods, limiting the investigation of SI‐ALI mechanisms. This study, for the first time, utilized organ‐on‐a‐chip and organoid technologies, optimizing chip design and precisely controlling smoke generation from non‐metallic materials to establish a human‐relevant, physiologically accurate model of fire‐related SI‐ALI. The results demonstrate that this model effectively simulates the alveolar‒capillary barrier and replicates key pathological features of lung injury, including oxidative stress, apoptosis, immune cell adhesion, inflammatory responses, capillary leakage, and mitochondrial damage. Injury responses of endothelial and epithelial cells to smoke exposure were thoroughly assessed at the organ level. Integrating proteomics and molecular biology techniques, along with comparisons to animal models, identified disease‐specific pathways related to the spliceosome and carbon metabolism, as well as pathogenic molecules such as catechol‐O‐methyltransferase (COMT) and nitrilase 1 (NIT1). Furthermore, molecular docking of COMT revealed potential therapeutic candidates from the FDA‐approved drug library, including Ractopamine HCl and Bimatoprost. The efficacy of intravenous vitamin C combined with nebulized budesonide was validated on the chip model, establishing a foundation for clinical applications. This study provides a robust model for investigating fire‐related SI‐ALI and offers novel insights into underlying mechanisms and therapeutic development.

Abstract Photocatalysts with dual functionalities of decomposing organic pollutants in water and combating bacterial infections are increasingly important. Herein, NaGdF4:Yb,Tm@ZnO/Ag3PO4 (UZA) nanoheterojunction photocatalysts were synthesized via hydrothermal, sol–gel, and in situ deposition methods. The UZA photocatalyst demonstrated exceptional efficiency in generating reactive oxygen species (ROS), crucial for organic pollutant degradation. The incorporation of Ag facilitated efficient charge transfer in the all‐solid‐state Z‐scheme nanoheterojunction system. Furthermore, UZA exhibited potent antibacterial properties against both Gram‐positive Staphylococcus aureus (S. aureus) and Gram‐negative Escherichia coli (E. coli). The minimum bactericidal concentrations (MBC) of UZA were 50 µg/mL for S. aureus and 25 µg/mL for E. coli under natural irradiation, and 100 µg/mL for S. aureus and 25 µg/mL for E. coli under 980 nm irradiation, respectively. In vivo studies using a mouse model of acute bacterial‐infected wounds demonstrated that UZA incorporated into chitosan hydrogel dressings accelerated wound healing through photodynamic therapy within 9 days. The treated wounds exhibited rapid reduction to 9.95% of the initial area, diminished inflammatory responses, and enhanced re‐epithelialization attributed to sustained antibacterial effects and pathogen inhibition. Moreover, UZA composites showed excellent biocompatibility with a minimal hemolysis rate of 0.5% on erythrocytes. These findings underscore the promising application of UZA in water treatment for organic pollutants and in the treatment of skin wound infections caused by pathogenic bacteria.

Abstract Over the recent years, fluorescence microscopy has seen substantial progress, transitioning from primarily qualitative analysis to a profoundly quantitative methodology, yet limitations in imaging depth and data quality persist due to tissue opacity. Tissue optical clearing (TOC) methodologies were implemented to overcome this hurdle, enabling the imaging and quantitative analysis of large tissue samples such as entire murine organs. Further improvements, including expansion microscopy merge TOC benefits with improved imaging resolution, converting cells and tissues into tissue‒gel hybrids. Yet, its intricate protocols lead to a remarkable, ∼10‒20× tissue volume expansion, making the acquisition of even thin sections exceedingly challenging in terms of time, labor, and data handling. Here, we present a novel solution, Improved Segmentation by gEntle Expansion (ISEE), for both TOC and gentle (1.6‒1.7×) tissue expansion for significantly improved precision of fluorescent signal segmentation, while maintaining tolerable increase during data acquisition in everyday laboratory practice. When applied to thick ∼40‒200 µm tissue slices, ISEE renders them transparent and ultimately expanded within minutes, in a simple, one‐step process compatible with immunohistochemistry as well as with all major murine organs.

Abstract Serological detection of syphilis‐specific antibodies is the most widely used clinical method for diagnosing syphilis. However, the current methods in clinical practice are too diverse, complicating result interpretation and wasting medical resources. To meet the resultant demand for a simple fast naked‐eye detection method, we employed the bacterial cell‐binding domain (CBD) of bacteriophage lysin to functionalize bio‐microparticles (engineered non‐culturable red‐colored Staphylococcus aureus bacteria), forming a bioprobe that can detect the syphilis‐specific antibodies from human serum in 5 min with naked eyes. Specifically, CBD is bioengineered by fusion with one of three antigens of the syphilis‐causing bacteria Treponema pallidum separately. The three resulting fusion proteins bind to the bacteria surface through the CBD motif, generating a bioprobe with the antigens exposed. When the bioprobe is added to the serum samples collected from the syphilis patients, the syphilis‐specific antibodies bind the antigens on the bioprobes and cross‐link them, forming eye‐visible red aggregates for the naked‐eye antibody detection. The bioprobe was validated on 209 clinical samples, revealing its high clinical sensitivity and specificity. Exploiting the natural biorecognition between the bacteria‐specific phage‐derived species and the phage host bacteria represents a promising strategy for producing facile probes for rapid point‐of‐care testing of infectious diseases.

Abstract Fluorescent dyes that emit in the second near‐infrared (NIR‐II, 1000–3000 nm) region have provided significant advances toward real‐time and high‐resolution imaging of vessel and lymphatic system. However, in vivo NIR‐II tracking of the fate of labeled cells still remains challenging. Here, we develop a shielding unit–donor–acceptor–donor–shielding unit (S‐D‐A‐D‐S) NIR‐II fluorophore (FE‐4ZW) with zwitterionic terminal groups for high‐efficiency cell labeling without using cell‐penetrating peptides, which provides for enhanced non‐invasive in vivo determination of the location of cell migration. The tethering terminal sulfoammonium inner salts are featured with its high affinity for cell membranes, thereby enabling the stable labeling even for fixed cells. The fate of transplanted stem cell and the tumor cell migration along lymphatic system in brain or periphery tissues are clearly monitored by the cell‐internalized FE‐4ZW. We also confirmed that a clinically used surfactant, D‐α‐tocopheryl polyethylene glycol‐1000 succinate, can reduce the liver and spleen uptake of FE‐4ZW. The fluorophore design strategy and cell‐labeling technology reported here open a new realm in the visualization of cell migration and insight into the relocation process, thereby ultimately providing an opportunity to investigate in greater detail of the underlying mechanisms of stem cell therapy and tumor metastasis.