Activation Mechanism of Fe2+ in Pyrrhotite Flotation: Microflotation and DFT Calculations.

In industrial manufacturing, pyrrhotite(Fe1-xS), once depressed, is commonly activated for flotation. However, the replacement of CuSO4 is necessary due to the need for exact control over the dosage during the activation of pyrrhotite, which can pose challenges in industrial settings. This research introduces the use of FeSO4 for the first time to efficiently activate pyrrhotite. The impact of two different activators on pyrrhotite was examined through microflotation experiments and density functional theory (DFT) calculations. Microflotation experiments confirmed that as the CuSO4 dosage increased from 0 to 8 × 10-4 mol/L, the recovery of pyrrhotite initially increased slightly from 71.27% to 87.65% but then sharply decreased to 16.47%. Conversely, when the FeSO4 dosage was increased from 0 to 8 × 10-4 mol/L, pyrrhotite's recovery rose from 71.27% to 82.37%. These results indicate a higher sensitivity of CuSO4 to dosage variations, suggesting that minor alterations in dosage can significantly impact its efficacy under certain experimental conditions. In contrast, FeSO4 might demonstrate reduced sensitivity to changes in dosage, leading to more consistent performance. Fe ions can chemically adsorb onto the surface of pyrrhotite (001), creating a stable chemical bond, thereby markedly activating pyrrhotite. The addition of butyl xanthate (BX), coupled with the action of Fe2+ on activated pyrrhotite, results in the formation of four Fe-S bonds on Fe2+. The proximity of their atomic distances contributes to the development of a stable double-chelate structure. The S 3p orbital on BX hybridizes with the Fe 3d orbital on pyrrhotite, but the hybrid effect of Fe2+ activation is stronger than that of nonactivation. In addition, the Fe-S bond formed by the addition of activated Fe2+ has a higher Mulliken population, more charge overlap, and stronger covalent bonds. Therefore, Fe2+ is an excellent, efficient, and stable pyrrhotite activator.

Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis.

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

Flotation Separation of Fluorite from Calcite using an Efficient Depressant Nitrilotriacetic Acid in the NaOL System.

Fluorite and calcite were separated with nitrilotriacetic acid (NTA) as a depressant. The single mineral flotation experiment confirmed that with 40 mg/L NaOL and 80 mg/L NTA, the fluorite recovery and calcite recovery were 24.37 and 94.13%, respectively, at pH 9. Meanwhile, in the fluorite-calcite binary mixed ore flotation experiment, the calcite recovery and fluorite recovery were 75.50 and 26.84%, respectively, and the CaCO3 and CaF2 grade in concentrate was 74.32 and 25.61%, respectively. The results confirmed that NTA could be used as a depressant to selectively inhibit fluorite flotation. The mechanism study illustrated that NTA was selectively reacted with fluorite by chemical interaction between O of NTA and Ca of fluorite. The adsorption of NTA on fluorite will impede the interaction between fluorite and NaOL. NTA could adsorb on fluorite in three ways, while the dominant two ways were the complex between double O of NTA and Ca of fluorite in a vertical model and the complex between double O of NTA and Ca of fluorite in a horizontal model.

Dual-targeting fucoidan-based microvesicle for arterial thrombolysis and re-occlusion inhibition.

Arterial thrombosis is a critical thrombotic disease that poses a significant threat to human health. However, the existing clinical treatment of arterial thrombosis lacks effective targeting and precise drug release capability. In this study, we developed a system for targeted delivery and on-demand release in arterial thrombosis treatment. The carrier was constructed using chitosan (CS) and fucoidan (Fu) through layer-by-layer assembly, with subsequent surface modification using cRGD peptide. Upon encapsulation of urokinase-type plasminogen activator (uPA), the resulting therapeutic drug delivery system, uPA-CS/Fu@cRGD, demonstrated dual-targeting abilities towards P-selectin and αIIbß3, as well as pH and platelet-responsive release properties. Importantly, we have demonstrated that the dual targeting effect exhibits higher targeting efficiency at shear rates simulating thrombosed arterial conditions (1800 s-1) compared to single targeting for the first time. In the mouse common iliac artery model, uPA-CS/Fu@cRGD exhibited great thrombolytic capability while promoting the down-regulation of coagulation factors (FXa and PAI-1) and inflammatory factors (TNF-α and IL-6), thus improving the thrombus microenvironment and exerting potential in preventing re-occlusion. Our dual-target and dual-responsive, fucoidan-based macrovesicle represent a promising platform for advanced drug target delivery applications, with potential to prevent coagulation tendencies as well as improving thrombolytic and reducing the risk of re-occlusion.

Facilely Prepared Thirsty Granules Arouse Tough Wet Adhesion on Overmoist Wounds for Hemostasis and Tissue Repair.

Bioadhesives have been widely used in hemostasis and tissue repair, but the overmoist and wet nature of wound surface (due to the presence of blood and/or wound exudate) has led to poor wet adhesion of bioadhesives, which interrupts the continuous care of wounds. Here, a thirsty polyphenolic silk granule (Tan@SF-pwd-hydro), which absorbs blood and exudate to self-convert to robust bioadhesives (Tan@SF-gel-hydro) in situ, was facilely developed in this study for enhanced wet adhesion toward hemostasis and tissue repair. Tan@SF-pwd-hydro could shield wounds' wetness and immediately convert itself to Tan@SF-gel-hydro to seal wounds for hemorrhage control and wound healing. The maximum adhesiveness of Tan@SF-gel-hydro over wet pigskin was as high as 59.8 ± 2.1 kPa. Tan@SF-pwd-hydro is a promising transformative dressing for hemostasis and tissue repair since its hemostatic time was approximately half of that of the commercial hemostatic product, CeloxTM, and its healing period was much shorter than that of the commercial bioadhesive product, TegadermTM. This pioneering study utilized adverse wetness over wounds to arouse robust adhesiveness by converting thirsty granules to bioadhesives in situ, creatively turning adversity into opportunities. The facile fabrication approach also offers new perspectives for manufacturing sustainability of biomaterials.

Chitosan/silk fibroin nanofibers-based hierarchical sponges accelerate infected diabetic wound healing via a HClO self-producing cascade catalytic reaction.

The diabetic chronic wound healing is extremely restricted by issues such as hyperglycemia, excessive exudate and reactive oxygen species (ROS), and bacterial infection, causing significant disability and fatality rate. Herein, the chitosan/silk fibroin nanofibers-based hierarchical 3D sponge (CSSF-P/AuGCs) with effective exudate transfer and wound microenvironment modulation are produced by integrating cascade reactor (AuGC) into sponge substrates with parallel-arranged microchannels. When applied to diabetic wounds, the uniformly parallel-arranged microchannels endow CSSF-P/AuGCs with exceptional exudate absorption capacity, keeping the wound clean and moist; additionally, AuGCs efficiently depletes glucose in wounds to generate H2O2, which is then converted into HClO via cascade catalytic reaction to eliminate bacterial infection and reduce inflammation. Experiments in vitro demonstrated that the antibacterial activity of CSSF-P/AuGCs against S. aureus and E. coli was 92.7 and 94.27 %, respectively. Experiments on animals indicated that CSSF-P/AuGC could cure wounds in 11 days, displaying superior wound-healing abilities when compared to the commercial medication Tegaderm™. This versatile CSSF-P/AuGCs dressing may be an attractive choice for expediting diabetic wound healing with little cytotoxicity, providing a novel therapeutic method for establishing a favorable pathological microenvironment for tissue repair.

Attenuation of NLRP3 Inflammasome by Cigarette Smoke is Correlated with Decreased Defense Response of Oral Epithelial Cells to Candida albicans.

BACKGROUND: It is well recognized that both smoke and Candida infection are crucial risk factors for oral mucosal diseases. The nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and its downstream effectors, interleukin (IL)-1ß and IL-18, are pivotal to the host defense against Candida and other pathogens. METHODS: The present study was designed to explore the effects of cigarette smoke and C. albicans on the NLRP3 inflammasome and its downstream signal pathway via in vitro cell model. Oral epithelial cells (Leuk-1 cells) were exposed to cigarette smoke extract (CSE) for 3 days and/or challenged with C. albicans. RESULTS: Microscopically, Leuk-1 cells exerted a defense response to C. albicans by markedly limiting the formation of germ tubes and microcolonies. CSE clearly eliminated the defense response of Leuk-1 cells. Functionally, CSE repressed NLRP3 inflammasome, and IL-1ß and IL-18 activation induced by C. albicans in Leuk-1 cells. CONCLUSION: Our results suggested that in oral epithelial cells, the NLRP3 inflammasome might be one of the target pathways by which CSE attenuates innate immunity and leads to oral disorders.

A sandwich-like silk fibroin/polysaccharide composite dressing with continual biofluid draining for wound exudate management.

Optimal wound healing requires a wet microenvironment without over-hydration. Inspired by capillarity and transpiration, we have developed a sandwich-like fibers/sponge dressing with continuous exudate drainage to maintain appropriate wound moisture. This dressing is prepared by integrating a three-layer structure using the freeze-drying method. Layer I, as the side that contacts with the skin directly, consists of a hydrophobic silk fibroin membrane; Layer II, providing the pumping action, is made of superabsorbent chitosan-konjac glucomannan sponge; Layer III, accelerating evaporation sixfold compared to natural evaporation, is constructed with a graphene oxide soaked hydrophilic cellulose acetate membrane. Animal experiments showed that the composite dressing had superior wound-healing characteristics, with wounds decreasing to 24.8% of their original size compared to 28.5% for the commercial dressing and 43.2% for the control. The enhanced wound healing can be ascribed to the hierarchical porous structure serves as the fluid-driving factor in this effort; the hydrophilicity of a membrane composed of silk fibroin nanofibers is adjustable to regulate fluid-transporting capacity; and the photothermal effect of graphene oxide guarantees exudates that have migrated to the top layer to evaporate continuously. These findings indicate the unidirectional wicking dressing has the potential to become the next generation of clinical dressings.

In situ generation of bioadhesives using dry tannic silk particles: a wet-adhesion strategy relying on removal of hydraulic layer over wet tissues for wound care.

Tissue adhesives have been widely used in biomedical applications. However, the presence of a hydrated layer on the surface of wet tissue severely hinders their adhesion capacities, resulting in ineffective wound treatment. To address this issue, a dry particle dressing (plas@SF/tann-hydro-pwd) capable of removing the hydrated layer and converting in situ to bioadhesives (plas@SF/tann-hydro-gel) was fabricated via simple physical mixing based on the hydrophobic-hydrogen bonding synergistic effect and Schiff-base reaction. It was found that the plas@SF/tann-hydro-gel bioadhesive, which was changed from plas@SF/tann-hydro-pwd dressing by adsorption of water, exhibited good wet adhesion to diverse biological tissues. In addition, the wet adhesion qualities of the plas@SF/tann-hydro-gel adhesive was studied under a variety of demanding conditions, including a wide range of temperatures, varying pH levels, highly concentrated salt solutions, and simulated fluids. Experiments on animals had showed that the adhesive plas@SF/tann-hydro-gel has superior wet adhesion qualities and superior wound healing properties compared to the commercial product Tegaderm™. This study develops a new wet-adhesion technique employing dry particle dressing to eliminate the hydrated layer over wet tissues for the in situ creation of gel bioadhesives for wound healing.

Dual modes reinforced silk adhesives for tissue repair: Integration of textiles and inorganic particles in silk gel for enhanced mechanical and adhesive strength.

Skin wound healing in dynamic environments remains challenging. Conventional gels are not ideal dressing materials for wound healing due to difficulties in completely sealing wounds and the inability to deliver drugs quickly and precisely to the injury. To tackle these issues, we propose a multifunctional silk gel that rapidly forms strong adhesions to tissue, has excellent mechanical properties, and delivers growth factors to the wound. Specifically, the presence of Ca2+ in the silk protein leads to a solid adhesion to the wet tissue through a chelation reaction with water-trapping behavior; the integrated chitosan fabric and CaCO3 particles ensure enhanced mechanical strength of the silk gel for better adhesion and robustness during wound repair; and the preloaded growth factor further promoted wound healing. The results showed the adhesion and tensile breaking strength were as high as 93.79 kPa and 47.20 kPa, respectively. MSCCA@CaCO3-aFGF could remedy the wound model in 13 days, with 99.41 % wound shrinkage without severe inflammatory responses. Due to strong adhesion properties and mechanical strength, MSCCA@CaCO3-aFGF can be a promising alternative to conventional sutures and tissue closure staples for wound closure and healing. Therefore, MSCCA@CaCO3-aFGF is expected to be a strong candidate for the next generation of adhesives.

Bioinspired Hemostatic Strategy via Pulse Ejections for Severe Bleeding Wounds.

Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings. Thus, multiple hemostatic strategies are critical for treating large bleeding wounds. In this study, inspired by bombardier beetles to eject toxic spray for defense, a shape-memory aerogel with an aligned microchannel structure was proposed, employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation. Bioinspired aerogels, after contact with blood, can rapidly expand inside the wound, offering robust physical barrier blocking, sealing the bleeding wound, and generating a spontaneous local chemical reaction causing an explosive-like generation of CO2 microbubbles, which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion. The ejection behavior, drug release kinetics, and permeation capacity were evaluated using a theoretical model and experimentally demonstrated. This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility, displaying great potential for clinical application in humans.

Catechol-chitosan/carboxymethylated cotton-based Janus hemostatic patch for rapid hemostasis in coagulopathy.

Uncontrolled bleeding is the leading cause of death, and the death risk of bleeding from coagulopathy is even higher. By infusing the relevant coagulation factors, bleeding in patients with coagulopathy can be clinically treated. However, there are not many emergency hemostatic products accessible for coagulopathy patients. In response, a Janus hemostatic patch (PCMC/CCS) with a two-layer structure of partly carboxymethylated cotton (PCMC) and catechol-grafted chitosan (CCS) was developed. Ultra-high blood absorption (4000 %) and excellent tissue adhesion (60 kPa) were both displayed by PCMC/CCS. The proteomic analysis revealed that PCMC/CCS has significantly contributed to the creative generation of FV, FIX, and FX, as well as to the substantial enrichment of FVII and FXIII, re-paving the initially blocked coagulation pathway of coagulopathy to promote hemostasis. The in vivo bleeding model of coagulopathy demonstrated that PCMC/CCS was substantially more effective than gauze and commercial gelatin sponge at achieving hemostasis in just 1 min. The study provides one of the first investigations on procoagulant mechanisms in anticoagulant blood conditions. Rapid hemostasis in coagulopathy will be significantly affected by the results of this experiment.

UArch: A Super-Resolution Processor With Heterogeneous Triple-Core Architecture for Workloads of U-Net Networks.

High-resolution medical images are of critical significance to improve disease diagnosis. Limited by the camera and power of medical devices, medical images often have very low resolution. For example, wireless capsule endoscopes, often used to diagnose diseases of the small bowel, can only capture low-resolution endoscopic images. The existing super-resolution (SR) networks perform exceptionally well in recovering high-resolution images, but they are computationally expensive and require high bandwidth, which can result in unacceptable latency and bandwidth requirements for embedded medical devices. In this paper, we propose a U-Net-based SR (USR) network structure and an SR processor named UArch. The USR-s, which is the lightweight version of USR, has an SR performance of 42.68 dB for ×2 scale SR. The USR-s has 0.3 dB higher PSNR (peak signal-to-noise ratio) than the SR algorithm, which is often used in recent SR hardware. Based on well-designed strategies, including heterogeneous triple-core architecture, fine-grained on-chip memory allocation, out-of-order execution, and sub-tensor-based processing flow, the UArch, designed for U-Net networks, can fulfill ×2, ×3, and ×4 scale SR by deploying USR-s, achieving high throughput of 60 fps and low latency of 25 ms for ×2 scale 1920 × 1080 output image SR at 156 MHz. The UArch achieves high energy efficiency which is 2264.5 GOPS/W when synthesized and evaluated under the TSMC 28 nm process and which is 199.3 GOPS/W when implemented on Xilinx ZCU111. Our SR processor is capable of reconstructing high-quality endoscopic images and is more efficient than the previous state-of-the-art SR processors.

Gas-jet propelled hemostats for targeted hemostasis in wounds with irregular shape and incompressibility.

Since hemostats are likely to be flushed off a wound by a massive gushing of blood, achieving rapid and effective hemostasis in complex bleeding wounds with powder hemostats continues to be a significant therapeutic challenge. In order to counter the flushing effect of gushing blood, a gas-jet propelled powder hemostat ((COL/PS)4@CaCO3-T-TXA+) has been developed. (COL/PS)4@CaCO3-T-TXA+ dives into the deep bleeding sites of complex wounds for targeted hemostasis. In preparation, protamine sulfate and collagen are first electrostatically deposited on CaCO3, which is then loaded with thrombin, and finally doped with protonated tranexamic acid (TXA-NH3+) to produce the final therapeutic medicine (COL/PS)4@CaCO3-T-TXA+. When applied to bleeding tissues, CaCO3 and TXA-NH3+ from (COL/PS)4@CaCO3-T-TXA+ immediately react with each other in blood to release countless CO2 macro-bubbles, which direct the hemostatic powder, (COL/PS)4@CaCO3-T-TXA+, precisely towards deep bleeding sites from complex wounds. Then the carried thrombin is released to accomplish targeted hemostasis. According to animal studies, (COL/PS)4@CaCO3-T-TXA+ has better effects in rabbit hepatic hemorrhage models; the hemorrhage quickly stops within 30 s, which is roughly 20% less than with the commercial product CeloxTM. The present study provides a new strategy for using powder hemostats to quickly and effectively stop bleeding in complex bleeding wounds.

Oral squamous cell carcinoma-derived EVs promote tumor progression by regulating inflammatory cytokines and the IL-17A-induced signaling pathway.

BACKGROUND: Inflammatory cytokines in the tumor microenvironment (TME) contribute to tumor growth, proliferation, and invasion, and tumor-derived extracellular vesicles (EVs) act as critical "messengers" of communication in the tumor microenvironment. The effects of EVs derived from oral squamous cell carcinoma (OSCC) cells on tumor progression and the inflammatory microenvironment are still unclear. Our study aims to investigate the role of OSCC-derived EVs in tumor progression, the imbalanced TME, and immunosuppression and their effect on the IL-17A-induced signaling pathway. METHODS: EVs were isolated from the supernatant of a mouse OSCC cell line, SCC7. The effects of SCC7-EVs and the EV release-specific inhibitor GW4869 on the proliferation and migration of SCC7 cells were investigated in vitro by using CCK-8 and scratch wound healing assays. RT-qPCR and ELISA were performed to examine the alterations in cytokine levels. Then, a mouse xenograft model of OSCC was established by submucosal injection of SCC7 cells with or without SCC7-EV and GW4869 treatment. The effects of GW4869 and SCC7-EVs on xenograft tumor proliferation and invasion were investigated by tumor volume determination and histopathological examination. ELISA was used to investigate the changes in serum cytokine levels. Immunohistochemistry was adopted to analyze the alterations in the levels of inflammatory cytokines, immune factors, and crucial molecules in the IL-17A signaling pathway. RESULTS: SCC7-derived EVs increased the supernatant and serum levels of IL-17A, IL-10, IL-1ß, and PD-L1, while GW4869 decreased those of TNF-α and IFN-γ. SCC7-EV treatment significantly increased xenograft tumor growth and invasion in mice but resulted in little liquefactive necrosis in tumors. However, GW4869 treatment significantly inhibited xenograft tumor growth but resulted in more liquefactive necrosis. SCC7-derived EVs decreased the expression level of PTPN2, suppressing the immune responses of CD8 + T cells in vivo. Moreover, SCC7-EV treatment significantly enhanced the tumor expression levels of crucial molecules in the IL-17A pathway, including IL-17A, TRAF6 and c-FOS, whereas GW4869 treatment significantly reduced those levels in tumor tissues. CONCLUSION: Our results indicated that OSCC-derived EVs can promote tumor progression by altering the TME, causing an inflammatory cytokine imbalance, inducing immunosuppression, and contributing to overactivation of the IL-17A-induced signaling pathway. Our study might provide novel insights into the role of OSCC-derived EVs in tumor biological behavior and immune dysregulation.

The Promotional Effect of GW4869 on C. albicans Invasion and Cellular Damage in a Murine Model of Oral Candidiasis.

Candida albicans (C. albicans) is one of the most common fungi in the human body; it is an opportunistic pathogen and can cause candidiasis. Extracellular vesicles (EVs) derived from the host cells have a potentially protective effect against pathogens and can be developed as vaccine formulations. GW4869 can inhibit the production and release of EVs. Previous studies have indicated that GW4869 can alter the immune and inflammatory responses of the host. However, the effect of GW4869 on Candida infection and the anti-Candida response of the host has not been investigated. We evaluated the effect of GW4869 on C. albicans invasion, biofilm formation, and cellular damage in a murine model of oral candidiasis. In this study, C. albicans-infected mice were injected with or without GW4869. The results proven by macroscopic, microscopic, and ultramicroscopic methods showed that GW4869 treatment exacerbated the oral candidiasis of mice, promoted C. albicans invasion and biofilm formation, and aggravated oral mucosal inflammation and cellular ultrastructural damage. The results are beneficial in the further exploration of the immune mechanism of C. albicans infection.

Oral Bacteriome and Mycobiome across Stages of Oral Carcinogenesis.

Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Numerous studies have focused on variations in the oral bacterial microbiota of patients with OSCC. However, similar studies on fungal microbiota, another integral component of the oral microbiota, are scarce. Moreover, there is an evidence gap regarding the role that microecosystems play in different niches of the oral cavity at different stages of oral carcinogenesis. Here, we catalogued the microbial communities in the human oral cavity by profiling saliva, gingival plaque, and mucosal samples at different stages of oral carcinogenesis. We analyzed the oral bacteriome and mycobiome along the health-premalignancy-carcinoma sequence. Some species, including Prevotella intermedia, Porphyromonas endodontalis, Acremonium exuviarum, and Aspergillus fumigatus, were enriched, whereas others, such as Streptococcus salivarius subsp. salivarius, Scapharca broughtonii, Mortierella echinula, and Morchella septimelata, were depleted in OSCC. These findings suggest that an array of signature species, including bacteria and fungi, are closely associated with oral carcinogenesis. OSCC-associated diversity differences, species distinction, and functional alterations were most remarkable in mucosal samples, not in gingival plaque or saliva samples, suggesting an urgent need to define oral carcinogenesis-associated microbial dysbiosis based on the spatial microbiome. IMPORTANCE Abundant oral microorganisms constitute a complex microecosystem within the oral environment of the host, which plays a critical role in the adjustment of various physiological and pathological states of the oral cavity. In this study, we demonstrated that variations in the "core microbiome" may be used to predict carcinogenesis. In addition, sample data collected from multiple oral sites along the health-premalignancy-carcinoma sequence increase our understanding of the microecosystems of different oral niches and their specific changes during oral carcinogenesis. This work provides insight into the roles of bacteria and fungi in OSCC and may contribute to the development of early diagnostic assays and novel treatments.

Antimicrobial Effect of Extracellular Vesicles Derived From Human Oral Mucosal Epithelial Cells on Candida albicans.

Candida albicans (C. albicans) is a commensal microorganism that colonizes the mucosal surfaces of healthy individuals. Changes in the host or environment can lead to overgrowth of C. albicans and infection of the host. Extracellular vesicles (EVs) are released by almost all cell types and play an increasingly recognized role in fighting microbial infection. The aim of the present study was to assess whether EVs derived from human oral mucosal epithelial (Leuk-1) cells can suppress the growth and invasion of C. albicans. The in vitro efficacy of Leuk-1-EVs against C. albicans was assessed by optical microscopy, laser scanning confocal microscopy, scanning electron microscopy, and transmission electron microscopy. The germ tube formation rate, the percentage of hyphae and the microcolony optical density were also used to analyze the growth of C. albicans in a coculture model with Leuk-1 cells and EVs or after inhibition of the secretion of EVs. A mouse model of oral candidiasis was established and submucosal injection of Leuk-1-EVs in the tongue was performed. Macroscopic observation, H&E staining, PAS staining, and scanning electron microscopy were used to assess antifungal effects of Leuk-1-EVs in vivo. The in vitro results showed that the growth of C. albicans was inhibited and that the morphology and ultrastructure were changed following Leuk-1-EVs treatment. The in vivo results exhibited that white lesions of the tongue, C. albicans infection, and oral mucosal inflammation of the infected mice were significantly alleviated after Leuk-1-EVs treatment. We thus reveal an antifungal capability of EVs derived from oral epithelial cells against C. albicans that is mediated by direct damage effects and potential synergy between EVs and human oral mucosal epithelial cells. This finding offers an intriguing, previously overlooked method of antifungal defense against C. albicans.

Dual-Driven Hemostats Featured with Puncturing Erythrocytes for Severe Bleeding in Complex Wounds.

Achieving rapid hemostasis in complex and deep wounds with secluded hemorrhagic sites is still a challenge because of the difficulty in delivering hemostats to these sites. In this study, a Janus particle, SEC-Fe@CaT with dual-driven forces, bubble-driving, and magnetic field- (MF-) mediated driving, was prepared via in situ loading of Fe3O4 on a sunflower sporopollenin exine capsule (SEC), and followed by growth of flower-shaped CaCO3 clusters. The bubble-driving forces enabled SEC-Fe@CaT to self-diffuse in the blood to eliminate agglomeration, and the MF-mediated driving force facilitated the SEC-Fe@CaT countercurrent against blood to access deep bleeding sites in the wounds. During the movement in blood flow, the meteor hammer-like SEC from SEC-Fe@CaT can puncture red blood cells (RBCs) to release procoagulants, thus promoting activation of platelet and rapid hemostasis. Animal tests suggested that SEC-Fe@CaT stopped bleeding in as short as 30 and 45 s in femoral artery and liver hemorrhage models, respectively. In contrast, the similar commercial product Celox™ required approximately 70 s to stop the bleeding in both bleeding modes. This study demonstrates a new hemostat platform for rapid hemostasis in deep and complex wounds. It was the first attempt integrating geometric structure of sunflower pollen with dual-driven movement in hemostasis.

Microcluster colloidosomes for hemostat delivery into complex wounds: A platform inspired by the attack action of torpedoes.

Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature, thereby causing massive blood loss and significantly increased mortality. Inspired by the attack action of torpedoes, we synthesized microcluster (MC) colloidosomes equipped with magnetic-mediated navigation and "blast" systems to deliver hemostats into the cavity of vase-type wounds. CaCO3/Fe2O3 (CF) microparticles functionalized with Arg-Gly-Asp (RGD) modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots (CDs) to form MC colloidosomes, which were loaded with thrombin and protonated tranexamic acid (TXA-NH3 +). The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH3 +. The CO2 bubbles generated during disassembly produced a "blast" that propelled thrombin into the wound cavity. Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within ∼60 s. Furthermore, in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes. This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis, creating a new paradigm for combating trauma treatment.