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Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.
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Hipertermia Inducida , Nanopartículas , Neoplasias , Animales , Ratones , Sistemas de Liberación de Medicamentos/métodos , Hipertermia Inducida/métodos , Fototerapia/métodos , Doxorrubicina , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , ADN/uso terapéutico , Concentración de Iones de Hidrógeno , Nanopartículas/uso terapéutico , Liberación de Fármacos , Línea Celular TumoralRESUMEN
Repair of DNA damage induced by ionizing radiation plays an important role in the cell response to ionizing radiation. Radiation-induced DNA damage also activates the p53 system, which determines the fate of cells. The kinetics of repair, which is affected by the cell itself and the complexity of DNA damage, influences the cell response and fate via affecting the p53 system. To mechanistically study the influences of the cell response to different LET radiations, we introduce a new repair module and a p53 system model with NASIC, a Monte Carlo track structure code. The factors determining the kinetics of the double-strand break (DSB) repair are modeled, including the chromosome environment and complexity of DSB. The kinetics of DSB repair is modeled considering the resection-dependent and resection-independent compartments. The p53 system is modeled by simulating the interactions among genes and proteins. With this model, the cell responses to low- and high-LET irradiation are simulated, respectively. It is found that the kinetics of DSB repair greatly affects the cell fate and later biological effects. A large number of DSBs and a slow repair process lead to severe biological consequences. High-LET radiation induces more complex DSBs, which can be repaired by slow processes, subsequently resulting in a longer cycle arrest and, furthermore, apoptosis and more secreting of TGFß. The Monte Carlo track structure simulation with a more realistic repair module and the p53 system model developed in this study can expand the functions of the NASIC code in simulating mechanical radiobiological effects.
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Roturas del ADN de Doble Cadena , Proteína p53 Supresora de Tumor , Daño del ADN , Reparación del ADN , Transferencia Lineal de Energía , Radiación Ionizante , Factor de Crecimiento Transformador beta/genética , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Mannosylerythritol lipids-A (MEL-A) is a novel biosurfactant with excellent surface activity and potential biomedical applications. In this study, we explored the antibacterial activity and the underlying mechanisms of MEL-A against the important food-borne pathogen Listeria monocytogenes. The bacterial growth and survival assays revealed a remarkable antibacterial activity of MEL-A. Since MEL-A is a biosurfactant, we examined the cell membrane integrity and morphological changes of MEL-A-treated bacteria by biochemical assays and flow cytometry analysis and electron microscopes. The results showed obvious damaging effects of MEL-A on the cell membrane and morphology. To further explore the antibacterial mechanism of MEL-A, a transcriptome analysis was performed, which identified 528 differentially expressed genes (DEGs). Gene ontology (GO) analysis revealed that the gene categories of membrane, localization and transport were enriched among the DEGs, and the analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways demonstrated significant changes in the maltodextrin ABC transporter system and stress response system. Furthermore, the growth of L. monocytogenes could also be significantly inhibited by MEL-A in milk, a model of a real food system, suggesting that MEL-A could be potentially applied as an natural antimicrobial agent to control food-borne pathogens in the food industry.
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Antibacterianos/farmacología , Glucolípidos/farmacología , Listeria monocytogenes/efectos de los fármacos , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Glucolípidos/química , Glucolípidos/aislamiento & purificación , Listeria monocytogenes/crecimiento & desarrollo , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: Clinical applications of FLASH radiotherapy require formulas to describe how the FLASH radiation features and other related factors determine the FLASH effect. Mathematical analysis of the models can connect the theoretical hypotheses with the radiobiological effect, which provides the foundation for establishing clinical application models. Moreover, experimental and clinical data can be used to explore the key factors through mathematical analysis. Approach: We abstract the complex models of the oxygen depletion hypothesis and radical recombination-antioxidants hypothesis into concise mathematical equations. The equations are solved to analyze how the radiation features and other factors influence the FLASH effect. Then we propose methodologies for determining the parameters in the models and utilizing the models to predict the FLASH effect. Main results: The formulas linking the physical, chemical and biological factors to the FLASH effect are obtained through mathematical derivation of the equation. The analysis indicates that the initial oxygen concentration, radiolytic oxygen consumption and oxygen recovery are key factors for the oxygen depletion hypothesis and that the level of antioxidants is the key factor for the radical recombination-antioxidants hypothesis. According to the model derivations and analysis, the methodologies for determining parameters and predicting the FLASH effect are proposed: the criteria for data filtration; the strategy of hybrid FLASH and conventional dose rate (CONV) irradiation to ensure the acquisition of effective experimental data across a wide dose range; pipelines of fitting parameters and predicting the FLASH effect. Significance: This study establishes the quantitative relationship between the FLASH effect and key factors. The derived formulas can be used to calculate the FLASH effect in future clinical FLASH radiotherapy. The proposed methodologies guide to obtain sufficient high-quality datasets and utilize them to predict FLASH effect. Furthermore, this study indicates the key factors of FLASH effect and offers clues to further explore the FLASH mechanism.
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In recent years, the immunomodulatory efficacy of Dendrobium officinale leaf polysaccharide (DOLP) has attracted much attention, but its potential immunomodulatory mechanism remains unclear. Therefore, we investigated the molecular mechanism of DOLP to ameliorate cyclophosphamide-induced immunosuppressed mice based on transcriptome profiling technology. The results indicated that DOLP significantly mitigated damage to immune organs, regulated the expression levels of inflammatory factors and immunoglobulins, and restored the balance of gut microbiota. Furthermore, it modulated metabolic pathways associated with the immune system, including antigen processing and presentation, hematopoietic cell line development, and natural killer cell-mediated cytotoxicity. DOLP might promote host hematopoietic function to enhance immune cell proliferation and differentiation by up-regulating Cd19, Cr2 and Il7r but down-regulating Dntt. DOLP also up-regulated the expression of MHC-1 (Gm11127, H2-K1, H2-Q10, H2-Q6, and H2-Q7), thus promoting antigen recognition by NK cells to enhance the innate immunity and helping T cells to deliver antigen and secrete immune factors so that enhancing the adaptive immunity.
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PURPOSE: Oxygen plays a crucial role in radiation biology. Antioxidants and peroxyl radicals affect the oxygen effect greatly. This study aims to establish a computational model of the oxygen effect and explore the effect attributed to antioxidants and peroxyl radicals. MATERIALS AND METHODS: Oxygen-related reactions are added to our track-structure Monte Carlo code NASIC, including oxygen fixation, chemical repair by antioxidants and damage migration from base-derived peroxyl radicals. Then the code is used to simulate the DNA damage under various oxygen, antioxidant and damage migration rate conditions. The oxygen enhancement ratio(OER) is calculated quantifying by the number of double-strand breaks for each condition. The roles of antioxidants and peroxyl radicals are examined by manipulating the relevant parameters. RESULTS AND CONCLUSIONS: Our results indicate that antioxidants are capable of rapidly restoring DNA radicals through chemical reactions, which compete with natural and oxygen fixation processes. Additionally, antioxidants can react with peroxyl radicals derived from bases, thereby preventing the damage from migrating to DNA strands. By quantitatively accounting for the impact of peroxyl radicals and antioxidants on the OER curves, our study establishes a more precise and comprehensive model of the radiation oxygen effect.
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Antioxidantes , Oxígeno , Antioxidantes/farmacología , Antioxidantes/química , Radicales Libres/química , Radicales Libres/efectos de la radiación , Método de Montecarlo , Peróxidos , ADN/efectos de la radiaciónRESUMEN
The severe electromagnetic (EM) interference and overheating issues in 5G/6G electric devices increasingly heighten the need for developing multifunctional materials with large heat conduction (HC) and high EM wave (EMW) absorption. Here, a series of γ-Al2O3-based yolk-shell microspheres (γ-AlOOH, γ-Al2O3, γ-Al2O3@C, γ-Al2O3@Fe3O4@C, and γ-Al2O3@FeAl2O4@Fe@C YSMSs) as multifunctional fillers are investigated for the simultaneous improvement in the HC and EMW absorption of γ-Al2O3-based composites. Using γ-AlOOH YSMSs as precursors produced from a hydrothermal method, the γ-Al2O3-based YSMSs were synthesized via an annealing route or soaking-annealing route; their phases, textures, and compositions were finely adjusted by changing the Al3+/Fe3+ molar ratio (ß) and annealing temperature (Ta). Results show that the thermal transfers in the γ-Al2O3-based YSMSs are promoted by the synergic effect of phonons and electrons when they are utilized as thermally conductive fillers. Comparatively, the γ-Al2O3@FeAl2O4@Fe@C YSMSs formed at ß = 8 : 2 and Ta = 700 °C exhibit a high HC of 1.84-3.29 W m-1 K-1 in a loading amount of 5-40%, exceeding those of not merely γ-Al2O3, γ-AlOOH, γ-Al2O3@C, and γ-Al2O3@Fe3O4@C YSMSs but also most previously reported fillers. Furthermore, the γ-Al2O3@Fe3O4@C YSMSs exhibit prominent EMW absorption properties with a large ABW/d of 4.49 GHz mm-1 (just 30% loading), superior to most other Al2O3-based absorbers. Such excellent EMW absorption could be explained by magnetic/dielectric dual loss and significant cavity and interfacial effects caused by yolk-shell structures. In conclusion, this work inspires the development of yolk-shell structures with magnetic/dielectric dual loss and phonon/electron thermal carriers as high-performance bifunctional materials with exceptional heat conduction and EMW absorption.
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Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.
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Disfunción Eréctil , Induración Peniana , Placa Aterosclerótica , Masculino , Humanos , Animales , Bovinos , Induración Peniana/cirugía , Pene , Disfunción Eréctil/etiología , Disfunción Eréctil/cirugía , Fibrosis , Placa AmiloideRESUMEN
Ursodeoxycholic acid (UDCA) is the preferred treatment for various types of cholestasis, however, its effectiveness is limited because of its insolubility in water. We used polyethylene glycol (PEG) and cationic polymer polyethylenimine (PEI) to double-modify graphite oxide (PPG) as a drug delivery system. UDCA was successfully loaded onto PPG through intermolecular interactions to form UDCA-PPG nanoparticles. UDCA-PPG nanoparticles not only improve the solubility and dispersibility of UDCA, but also have good biocompatibility and stability, which significantly improve the delivery rate of UDCA. The results indicated that UDCA-PPG significantly reduced ROS levels, promoted cell proliferation, protected mitochondrial membrane potential, reduced DNA damage and reduced apoptosis in the DCA-induced cell model. In a mouse cholestasis model established by bile duct ligation (BDL), UDCA-PPG improved liver necrosis, fibrosis, and mitochondrial damage and reduced serum ALT and AST levels, which were superior to those in the UDCA-treated group. UDCA-PPG reduced the expression of the apoptosis-related proteins, Caspase-3 and Bax, increased the expression of Bcl-2, and reduced the expression of the oxidative stress-related proteins, NQO and HO-1, as well as the autophagy-related proteins LC3, p62 and p-p62. Therefore, UDCA-PPG can enhance the therapeutic effect of UDCA in cholestasis, by significantly improving drug dispersibility and stability, extending circulation time in vivo, promoting absorption, decreasing ROS levels, enhancing autophagy flow and inhibiting apoptosis via the Bcl-2/Bax signaling pathway.
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Apoptosis , Colestasis , Grafito , Hepatocitos , Nanocompuestos , Ácido Ursodesoxicólico , Grafito/química , Grafito/farmacología , Ácido Ursodesoxicólico/farmacología , Ácido Ursodesoxicólico/química , Animales , Apoptosis/efectos de los fármacos , Nanocompuestos/química , Ratones , Colestasis/tratamiento farmacológico , Colestasis/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Polietileneimina/química , Polietileneimina/farmacología , HumanosRESUMEN
Intestinal immunity plays a pivotal role in overall immunological defenses, constructing mechanisms against pathogens while maintaining balance with commensal microbial communities. Existing therapeutic interventions may lead to drug resistance and potential toxicity when immune capacity is compromised. Dendrobium officinale, a traditional Chinese medicine, contains components identified to bolster immunity. Employing network pharmacology strategies, this study identified constituents of Dendrobium officinale and their action targets in the TCMSP and Swiss Target Prediction databases, and compared them with intestinal immunity-related targets. Protein-protein interaction networks revealed the core targets of Dendrobium officinale polysaccharides, encompassing key pathways such as cell proliferation, inflammatory response, and immune reactions, particularly in association with the Toll-like receptor 4. Molecular docking and molecular dynamics simulation further confirmed the high affinity and stability between Dendrobium officinale polysaccharides and Toll-like receptor 4. In vivo experiments demonstrated that Dendrobium officinale polysaccharides modulates the expression of Toll-like receptor 4 and its downstream key proteins in the colonic mucosa of mice. Consequently, these findings suggest that Dendrobium officinale polysaccharides may serve as a potential modulator for intestinal immune functions, with its mechanism potentially related to the Toll-like receptor 4.
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Dendrobium , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Polisacáridos , Receptor Toll-Like 4 , Dendrobium/química , Polisacáridos/farmacología , Polisacáridos/química , Animales , Ratones , Receptor Toll-Like 4/metabolismo , Farmacología en Red , Mapas de Interacción de Proteínas/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Masculino , Intestinos/efectos de los fármacos , Intestinos/inmunologíaRESUMEN
Dendrobium officinale is widely consumed owing to its numerous beneficial effects. We aimed to characterize polysaccharides of Dendrobium officinale (DOP) from the stems of Dendrobium officinale Xianhu 2 and clarify whether it benefit the intestinal microbiota and the immune system. The DOP weighed 291 kDa and comprised mannose, glucose, galactose, and rhamnose at 59.31:33.31:1.00:0.51 M ratio. In in vitro/vivo studies, DOP significantly increased benign intestinal microbe proportion (Lactobacillus, etc.), but reduced harmful bacteria (Escherichia_Shigella) (P < 0.05), and significantly increased butyric acid production (P < 0.05). Concentrations of 2 g/L DOP for in vitro fermentation and 100 mg/kg body weight for the mouse model were effective. In mice, DOP significantly reduced CRP, CD3, CD4, and TNF-α levels and increased C4 levels (P < 0.05). DOP might influence the immune system indirectly through regulation of the gut microbiota. Its possible regulation mechanism was that DOP reduced CD4+ Th cells proliferation so that reduced the secretion of TNF-α.
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Dendrobium , Microbioma Gastrointestinal , Ratones , Animales , Manosa , Factor de Necrosis Tumoral alfa , Galactosa , Ramnosa , Ácido Butírico , Polisacáridos , Carbohidratos de la Dieta , Glucosa , Sistema InmunológicoRESUMEN
PURPOSE: FLASH (ultra-high dose rate) radiotherapy spares normal tissue while keeping tumor control. However, the mechanism of the FLASH effect remains unclear and may have consequences beyond the irradiated area. MATERIALS AND METHODS: We reanalyze the available results of ultra-high-dose-rate-related experiments to find out the key points of the mechanism of the FLASH effect. Then, we present a hypothesis on the mechanism of the FLASH effect: FLASH beams generate a high transient concentration of peroxyl radicals leading to a high fraction of radical recombination, which results in less oxidation damage to normal tissue. For the cells containing higher concentrations of antioxidants, the fractions of radical recombination are smaller because the antioxidants compete to react with peroxyl radicals. Therefore the damages by different dose rate beams differ slightly in this condition. Since some tumors contain a higher level of antioxidants, this may be the reason for the loss of the protective effect in tumors irradiated by FLASH beams. The high concentration of antioxidants in tumors results in slight radiolytic oxygen consumption, and consequently the protective effect observed in in vitro experiment cannot be observed in in vivo experiment. To quantitatively elaborate our hypothesis, a kinetic model is implemented to simulate the reactions induced by irradiation. Two parameters are defined to abstractly study the factors affecting the reaction, such as dose rate, antioxidants, total dose and reaction rate constants. RESULTS AND CONCLUSIONS: We find that the explanation of the difference between in vivo and in vitro experiments is crucial to understanding the mechanism of the FLASH effect. Our hypothesis agrees with the results of related experiments. Based on the kinetic model, the effects of these factors on the FLASH effect are quantitatively investigated.
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Antioxidantes , Peróxidos , Antioxidantes/metabolismo , Estrés Oxidativo , Etopósido , Recombinación Genética , Dosificación RadioterapéuticaRESUMEN
The development of novel prebiotics, which could regulate the intestinal microbiota, may help prevent and treat intestinal diseases. Here, we studied a homogeneous polysaccharide, LPE-2, produced by Lactobacillus pentosus YY-112 during fermentation. Methylation and gas chromatography-mass spectrometry analysis, combined with nuclear magnetic resonance results, suggested that the structural unit of LPE-2 comprises a branched mannan moiety and a linear glucan moiety. In vitro simulated intestinal fermentation showed that LPE-2 reduced harmful intestinal gas production and promoted short-chain fatty acid production (especially propionic acid). Moreover, it reduced the relative abundance of Escherichia-Shigella, increased that of Bifidobacterium and Lactobacillus, and had a stronger regulatory effect on intestinal flora in women than in men. The potential sex-specific prebiotic effects of LPE-2 on human intestinal health, were possibly related to its mannan branch with (1â2) and (1â3) linkages and backbones with flexible α configurations, which are sheared and degraded/utilized easier by Bifidobacterium and Lactobacillus.
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Microbioma Gastrointestinal , Lactobacillus pentosus , Masculino , Humanos , Femenino , Mananos/farmacología , Heces/microbiología , Prebióticos/análisis , Lactobacillus , FermentaciónRESUMEN
Photothermal therapy (PTT) is considered a promising treatment for tumors; however, its efficacy is restricted by heat shock proteins (HSPs). Herein, a stimuli-responsive theranostic nanoplatform (M/D@P/E-P) is designed for synergistic gas therapy and PTT. This nanoplatform is fabricated by a load of manganese carbonyl (MnCO, CO donor) in dendritic mesoporous silicon (DMS), followed by the coating with polydopamine (PDA) and loading of epigallocatechin gallate (EGCG, HSP90 inhibitor). Upon near-infrared (NIR) irradiation, the photothermal effect of PDA can kill tumor cells and allow for the controlled drug release of MnCO and EGCG. Moreover, the acidity and H2 O2 -rich tumor microenvironment enable the decomposition of the released MnCO, accompanied by the production of CO. CO-initiated gas therapy can realize to disrupt the mitochondrial function, which will accelerate cell apoptosis and down-regulate HSP90 expression by decreasing intracellular ATP. The combination of EGCG and MnCO can significantly minimize the thermo-resistance of tumors and improve PTT sensitivity. In addition, the released Mn2+ enables T1 -weighted magnetic imaging of tumors. The therapeutic efficacy of the nanoplatform is methodically appraised and validated both in vitro and in vivo. Taken together, this study affords a prime paradigm for applying this strategy for enhanced PTT via mitochondrial dysfunction.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Fototerapia/métodos , Biomimética , Preparaciones de Acción Retardada , Neoplasias/patología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Antioxidant-defense systems of tumor cells protect them from oxidative damage and is strongly associated with tumor metastasis. In this work, a mussel-inspired multifunctional nanomedicine (ZS-MB@P) has been designed for inhibiting tumor growth and metastasis through amplified oxidative stress and photothermal/magnetothermal/photodynamic triple-combination therapy. This nanomedicine was fabricated via loading a silica shell on the magnetic nano-octahedrons [zinc-doped magnetic Fe3O4 nano-octahedrons] by encapsulating photosensitizer methylene blue (MB) and subsequently coating polydopamine (PDA) shells as "gatekeeper." The nanomedicine could realize photothermal therapy, photodynamic therapy, and magnetic hyperthermia after treatment with near-infrared (NIR) irradiation and applied magnetic field. Under pH and NIR stimulation, controlled amount of MB was released to produced exogenous reactive oxygen species. Noteworthy, PDA can amplify intracellular oxidative stress by depleting glutathione, thus inhibiting breast cancer metastasis effectively since oxidative stress is an important barrier to tumor metastasis. The outstanding ability to suppress tumor growth and metastasis was comprehensively assessed and validated both in vitro and in vivo. Moreover, the nanomedicine showed outstanding T2 magnetic resonance imaging for tracking the treatment process. Taken together, this work offers an innovative approach in the synergistic treatment of recalcitrant breast cancer.
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Neoplasias de la Mama , Hipertermia Inducida , Nanopartículas , Fotoquimioterapia , Humanos , Femenino , Fotoquimioterapia/métodos , Fototerapia , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Estrés Oxidativo , Línea Celular Tumoral , Nanomedicina TeranósticaRESUMEN
Industrial internet security is a critical component of cyberspace safety. Furthermore, the encryption protocol is a critical component of cyberspace security. Due to the rapid development of industrial internet and edge computing, increasingly more devices are outsourcing their data to cloud servers to save costs. Edge devices should have a secure session key to reduce communication costs and share information. However, most key generation and storage are completed by a centralized third-party organization, which carries some security risks. In this context, this paper will propose a lightweight multi-dimensional virtual iteration of the group key agreement protocol. Group key agreement protocol allows for one-at-a-time encryption and timely key updates without the involvement of a trusted third party, and each device in the network can agreement a large number of keys. According to the analysis of this protocol, it has high security, rapid computation speed, and little storage space.
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Seguridad Computacional , Servicios Externos , Nube Computacional , Internet , ComunicaciónRESUMEN
Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.
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Background: The incidence of hepatic artery thrombosis in pediatric living donor liver transplantation (LDLT) is significantly higher than that in adults, and is closely related to the surgeon's experience with hepatic artery anastomosis. However, there are few studies on the learning curve of hepatic artery anastomosis among surgeons. Methods: We collected data related to 75 patients who underwent pediatric LDLT and hepatic artery anastomosis independently by the same surgeon. Cumulative sum method (CUSUM) was used to analyse the duration of hepatic artery anastomosis and determine the cut-off value. Patients were divided into two phases according to CUSUM. We analysed the intraoperative and postoperative data and survival outcomes of the included patients. Results: Total anastomosis duration decreased with an increased number of completed procedures, and the average duration was 42.4 ± 2.20â min. A cut-off value and two phases were identified: 1-43 cases and 44-75 cases. Intraoperative blood loss was significantly lower in phase 2 than in phase 1. The immediate functional changes of total bilirubin (TBIL) and direct bilirubin (DBIL) were significantly also lower in phase 2 than in phase 1. Other functional outcomes, postoperative complications, and the long-term survival rate were not significantly different between the two phases. Conclusions: Technical competence in pediatric LDLT hepatic artery anastomosis may be achieved after completing 43 cases. It is a safe procedure with a surgical loupe that can be systematized and adopted by pediatric surgeons with sufficient experience via a relatively long learning curve.
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Dendrobium officinale is widely used as a health supplement, but its specific impact on healthy gut microbiota has not yet been clarified, nor has its impact on different human genders. To overcome the problems mentioned above. DOP was extracted and purified with an 8000-12,000 Da dialysis bag. The molecular weight and monosaccharide composition were determined using HPGPC and GC. Gas chromatography was used to detect the content of SCFA. 16S rDNA sequencing was used to analyze the diversity of human microbiota. The results showed that DOP contained two fractions, with an average molecular weight of 277 kDa and 1318 Da, and mainly composed of mannose and glucose. DOP can increase the relative abundance of benign microbiota and decrease the harmful types. Propionic acid content in women was significantly increased after DOP treatment. Finally, the correlation analysis revealed that DOP was beneficial to the microbiota of both men and women. It can be concluded from the results that DOP is a health supplement suitable for humans, and especially women.
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Exopolysaccharides (EPSs) derived from Lactobacilli have important physiological effects and are commonly used as new prebiotics. We identified and studied a new Lactobacillus strain, YY-112, isolated from waxberry (Myrica rubra). This strain, identified as Lactobacillus pentosus, tolerates acids, bile salts, and artificial digestive fluids. The EPS derived from this strain weighed 5.9 × 104 Da and contained glucose, mannose, glucosamine, galactose, and rhamnose at 62.69 : 85.85 : 2.46 : 2.92 : 1.00 molar ratios. We found that the EPS from this strain increased the ratio of Bacteroidetes to Firmicutes and decreased the relative abundance of Proteobacteria, especially Escherichia-Shigella, when added to a simulated gastrointestinal system in vitro. After analysing the short-chain fatty acids, we found that this EPS promoted the production of acetic acid, propionic acid, and butyric acid, and reduced the ratio of acetic acid to propionic acid. We conclude that Lactobacillus pentosus YY-112 is a potential probiotic strain with EPS that is beneficial for the intestinal microbiota and short-chain fatty acid production.