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Environmental heterogeneity partly drives microbial succession in arthropods, while the microbial assembly mechanisms during environmental changes remain largely unknown. Here, we explored the temporal dynamics and assembly mechanisms within both bacterial and fungal communities in Liriomyza huidobrensis (Blanchard) during the transition from field to laboratory conditions. We observed a decrease in bacterial diversity and complexity of bacterial-fungal co-occurrence networks in leaf miners transitioning from wild to captive environments. Both neutral and null models revealed that stochastic processes, particularly drift (contributing over 70%), play a crucial role in governing bacterial and fungal community assembly. The relative contribution of ecological processes such as dispersal, drift, and selection varied among leaf miners transitioning from wild to captive states. Furthermore, we propose a hypothetical scenario for the assembly and succession of microbial communities in the leaf miner during the short- and long-term transition from the wild to captivity. Our findings suggest that environmental heterogeneity determines the ecological processes governing bacterial and fungal community assembly in leaf miners, offering new insights into microbiome and mycobiome assembly mechanisms in invasive pests amidst environmental change.
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Cognitive impairment associated with diabetes and Alzheimer's disease has become a major health issue affecting older individuals, with morbidity rates growing acutely each year. Ferroptosis is a novel form of cell death that is triggered by iron-dependent lipid peroxidation. A growing body of evidence suggests a strong correlation between the progression of cognitive impairment and diabetes, Alzheimer's disease, and ferroptosis. The pharmacological modulation of ferroptosis could be a promising therapeutic intervention for cognitive impairment associated with diabetes and Alzheimer's disease. In this review, we summarize evidence on ferroptosis in the context of cognitive impairment associated with diabetes and Alzheimer's disease and provide detailed insights into the function and potential action pathways of ferroptosis. Furthermore, we discuss the therapeutic importance of natural ferroptosis products in improving the cognitive impairment associated with diabetes and Alzheimer's disease and provide new insights for clinical treatment.
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Arthropods harbor complex microbiota that play a pivotal role in host fitness. While multiple factors, like host species and diet, shape microbiota in arthropods, their impact on community assembly in wild insects remains largely unknown. In this study, we surveyed bacterial and fungal community assembly in nine sympatric wild insect species that share a common citrus fruit diet. Source tracking analysis suggested that these insects acquire some bacteria and fungi from the citrus fruit with varying degrees. Although sharing a common diet led to microbiota convergence, the diversity, composition, and network of both bacterial and fungal communities varied significantly among surveyed insect groups. Null model analysis indicated that stochastic processes, particularly dispersal limitation and drift, are primary drivers of structuring insect bacterial and fungal communities. Importantly, the influence of each community assembly process varied strongly depending on the host species. Thus, we proposed a speculative view that the host specificity of the microbiome and mycobiome assembly is widespread in wild insects despite sharing the same regional species pool. Overall, this research solidifies the importance of host species in shaping microbiomes and mycobiomes, providing novel insights into their assembly mechanisms in wild insects. IMPORTANCE: Since the microbiome has been shown to impact insect fitness, a mechanistic understanding of community assembly has potentially significant applications but remains largely unexplored. In this paper, we investigate bacterial and fungal community assembly in nine sympatric wild insect species that share a common diet. The main findings indicate that stochastic processes drive the divergence of microbiomes and mycobiomes in nine sympatric wild insect species. These findings offer novel insights into the assembly mechanisms of microbiomes and mycobiomes in wild insects.
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Microglia, as immune cells in the central nervous system, are closely related to cognitive impairment associated with type 2 diabetes (T2D). Preliminary explorations have investigated the relationship between T2D-related cognitive impairment and the activation and polarization of microglia. This review summarizes the potential mechanisms of microglial activation and polarization in the context of T2D. It discusses central inflammatory responses, neuronal apoptosis, amyloid-ß deposition, and abnormal phosphorylation of Tau protein mediated by microglial activation and polarization, exploring the connections between microglial activation and polarization and T2D-related cognitive impairment from multiple perspectives. Additionally, this review provides references for future treatment targeting microglia in T2D-related cognitive impairment and for clinical translation.
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Indoleamine-2,3-dioxygenase-1 (IDO1) pathogenically suppresses immune cell infiltration and promotes tumor cell immune escape by overmetabolizing tryptophan to N-formyl kynurenine in the tumor microenvironment (TME). However, it remains challenging for IDO1 immune checkpoint inhibitors to achieve a significant potency of progression-free survival. Here, we developed a breakthrough in IDO1 inhibition by sono-targeted biobromination reaction using immunostimulating hypobromic-P-phenylperoxydibenzoic acid-linked metallic organic framework nanomedicine (H-MOF NM) to remodel the TME from debrominated hypoxia into hypobromated normoxia and activate the IDO1 immune pathway with in vitro and in vivo remarkable antitumor efficacy. H-MOF NM contains Br+ and O- active ingredients with an enlarged band gap to deactivate IDO1 through an innovative biochemical mechanism, taking control over brominating IDO1 amino acid residues at the active sites in the remodeled TME and subsequently activating the immune response, including DC maturation, T-cell activation, and macrophage polarization. Importantly, the H-MOF NM achieves multiple immune responses with high tumor regression potency by combination sono-immunotherapy. This study describes an excellent IDO1 inhibition strategy through the development of immune biobrominative H-MOF nanomedicine and highlights efficient combination immunotherapy for tumor treatment.
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Fe single atoms (Fe SAs) based catalysts have received much attention in electrocatalytic oxygen reduction reaction (ORR) due to its low-cost and high activity. Yet, the facile synthesis of efficient and stable Fe SAs catalysts are still challenging. Here, we reported a Fe SAs anchored on N-doped mesoporous carbon microspheres (NC) catalyst via spraying drying and pyrolysis processes. The highly active Fe SAs are uniformly distributed on the NC matrix, which prevented the aggregation benefiting from the enhanced Fe-N bonds. Also, the mesoporous carbon structure is favorable for fast electron and mass transfer. The optimized Fe@NC-2-900 catalyst shows positive half wave potential (E1/2 = 0.86 V vs reversible hydrogen electrodes (RHE)) and starting potential (Eonset = 0.98 V vs RHE) in ORR, which is comparable to the commercial Pt/C catalyst (E1/2= 0.87 V, Eonset = 1.08 V). Outstanding stability with a current retention rate of 92.5% for 9 hours and good methanol tolerance are achieved. The assembled zinc-air batteries showed good stability up to 500 hours at a current density of 5 mA cm-2. This work shows potentials of Fe SAs based catalysts for the practical application in ORR and pave a new avenue for promoting their catalytic performances.
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Hypoxic-ischemic encephalopathy (HIE) is a brain injury induced by many causes of cerebral tissue ischemia and hypoxia. Although HIE may occur at many ages, its impact on the neonatal brain is greater because it occurs during the formative stage. Recent research suggests that histone modifications may occur in the human brain in response to acute stress events, resulting in transcriptional changes and HIE development. Because there are no safe and effective therapies for HIE, researchers have focused on HIE treatments that target histone modifications. In this review, four main histone modifications are explored, histone methylation, acetylation, phosphorylation, and crotonylation, as well as their relevance to HIE. The efficacy of histone deacetylase inhibitors in the treatment of HIE is also explored. In conclusion, targeting histone modifications may be a novel strategy for elucidating the mechanism of HIE, as well as a novel approach to HIE treatment.
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This video vignette illustrates the application of the da Vinci Xi® robotic platform for robotic left colectomy and intracorporeal overlap anastomosis in a 51-year-old patient diagnosed with sigmoid-descending colon junction cancer. Emphasizing the advantages of robotic surgery in colorectal procedures, the video showcases a complete mesocolic excision, involving steps such as medial-to-lateral dissection, mobilization of the splenic flexure, ligation of the left colic and sigmoid arteries, and resection of an abdominal wall nodule. The presentation highlights the surgical precision and efficiency achieved, including minimal blood loss and no complications, with an operation time of 190 min. The postoperative outcome was favorable, with the patient discharged on the eighth day and subsequent management involving chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for stage pT4bN1aM1c moderately differentiated adenocarcinoma. This case underscores the enhanced capabilities of robotic platforms in complex colorectal surgeries, particularly in achieving cytoreductive surgery (CRS) and ensuring anastomosis safety with improved R0 resection rates.
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Anastomose Cirúrgica , Colectomia , Procedimentos Cirúrgicos Robóticos , Neoplasias do Colo Sigmoide , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Colectomia/métodos , Pessoa de Meia-Idade , Anastomose Cirúrgica/métodos , Neoplasias do Colo Sigmoide/cirurgia , Adenocarcinoma/cirurgia , Masculino , Colo Descendente/cirurgiaRESUMO
Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.
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Carcinoma Hepatocelular , Ferroptose , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Ferroptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologiaRESUMO
OBJECTIVE: Non-invasive biomarkers have recently shown promise for seizure forecasting in people with epilepsy. In this work, we developed a seizure-day forecasting algorithm based on nocturnal sleep features acquired using a smart shirt. METHODS: Seventy-eight individuals with epilepsy admitted to the Centre hospitalier de l'Université de Montréal epilepsy monitoring unit wore the Hexoskin biometric smart shirt during their stay. The shirt continuously measures electrocardiography, respiratory, and accelerometry activity. Ten sleep features, including sleep efficiency, sleep latency, sleep duration, time spent in non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM), wakefulness after sleep onset, average heart and breathing rates, high-frequency heart rate variability, and the number of position changes, were automatically computed using the Hexoskin sleep algorithm. Each night's features were then normalized using a reference night for each patient. A support vector machine classifier was trained for pseudo-prospective seizure-day forecasting, with forecasting horizons of 16- and 24-h to include both diurnal and nocturnal seizures (24-h) or diurnal seizures only (16-h). The algorithm's performance was assessed using a nested leave-one-patient-out cross-validation approach. RESULTS: Improvement over chance (IoC) performances were achieved for 48.7% and 40% of patients with the 16- and 24-h forecasting horizons, respectively. For patients with IoC performances, the proposed algorithm reached mean IoC, sensitivity and time in warning of 34.3%, 86.0%, and 51.7%, respectively for the 16-h horizon, and 34.2%, 64.4% and 30.2%, respectively, for the 24-h horizon. SIGNIFICANCE: Smart shirt-based nocturnal sleep analysis holds promise as a non-invasive approach for seizure-day forecasting in a subset of people with epilepsy. Further investigations, particularly in a residential setting with long-term recordings, could pave the way for the development of innovative and practical seizure forecasting devices. PLAIN LANGUAGE SUMMARY: Seizure forecasting with wearable devices may improve the quality of life of people living with epilepsy who experience unpredictable, recurrent seizures. In this study, we have developed a seizure forecasting algorithm using sleep characteristics obtained from a smart shirt worn at night by a large number of hospitalized patients with epilepsy (78). A daily seizure forecast was generated following each night using machine learning methods. Our results show that around half of people with epilepsy may benefit from such an approach.
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OBJECTIVE: To explore the effect and anxiolytic mechanism of a natural remedy called Fructus gardeniae (FG). METHODS: The elevated-plus maze (EPM) test was used to confirm the anxiolytic effect of FG. The potential and anxiolytic components, targets, and route processes of FG were investigated using the network pharmacology method in conjunction with metabolomics and molecular docking technologies. RESULTS: FG could greatly enhance the proportion of time and times of opening arms, according to the EPM data. As to the metabolomics findings, a total of 61 distinct metabolites were found, mainly involved in glycine, serine, and threonine metabolism as well as alanine, aspartate, and glutamate metabolism. The primary active ingredients of FG, nicotiflorin, jasminodiol, and crocetin, demonstrated substantial binding affinities with monoamine oxidase A (MAOA), monoamine oxidase A (ACHE), malate dehydrogenase 2 (MDH2), glutamate decarboxylase 2 (GAD2), glutamate decarboxylase 1 (GAD1), and nitric oxide synthase (NOS1), according to the findings of network pharmacology and molecular docking. CONCLUSION: FG exerts an anxiolytic action via targeting MAOA, ACHE, MDH2, GAD2, GAD1, and NOS1, and regulating the metabolism of glycine, serine, and threonine as well as alanine, aspartic acid, and glutamic acid.
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Most patients experience postoperative ileus (POI) after surgery, which is associated with increased morbidity, mortality, and hospitalization time. POI is a consequence of mechanical damage during surgery, resulting in disruption of motility in the gastrointestinal tract. The mechanisms of POI are related to aberrant neuronal sensitivity, impaired epithelial barrier function, and increased local inflammation. However, the details remain enigmatic. Therefore, experimental murine models are crucial for elucidating the pathophysiology and mechanism of POI injury and for the development of novel therapies. Here, we introduce a murine model of POI generated via intestinal manipulation (IM) that is similar to clinical surgery; this is achieved by mechanical damage to the small intestine by massaging the abdomen 1-3 times with a cotton swab. IM delayed gastrointestinal transit 24 h after surgery, as assessed by FITC-dextran gavage and fluorescence detection of the segmental digestive tract. Moreover, tissue swelling of the submucosa and immune cell infiltration were investigated by hematoxylin and eosin staining and flow cytometry. Proper pressure of the IM and a hyperemic effect on the intestine are critical for the procedure. This murine model of POI can be utilized to study the mechanisms of intestinal damage and recovery after abdominal surgery.
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Modelos Animais de Doenças , Íleus , Complicações Pós-Operatórias , Animais , Íleus/etiologia , Camundongos , Complicações Pós-Operatórias/etiologia , Intestino Delgado , Camundongos Endogâmicos C57BL , MasculinoRESUMO
Two π-conjugated covalent organic frameworks (COFs) with nonring imine or benzoxazole ring linkages were prepared by reacting 3,3'-dihydrooxybenzidine (BDOH) with 3,5-triformylbenzene (Tb) in the presence or absence of benzimidazole (BDOH-Tb-IM and BDOH-Tb-BO). Although two COFs indicated similar composition, crystalline structures, and morphologies, imine-based BDOH-Tb-IM exhibited a photocatalytic H2O2 production rate of 2490 µmol·g-1·h-1 in sacrificial reagent-free pure water, higher than that of benzoxazole-based BDOH-Tb-BO-a (1168 µmol·g-1·h-1). The higher photocatalytic activity of BDOH-Tb-IM was attributed to its more efficient photoinduced charge separation and utilization efficiency and different 2e- ORR active sites over the two COFs. This study demonstrated an available ring effect to adjust photocatalytic performance between π-conjugated COFs.
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Silicosis, caused by silica exposure, is the most widespread and deadliest occupational disease. However, effective treatments are lacking. Therefore, it is crucial to elucidate the mechanisms and targets involved in the development of silicosis. We investigated the basic processes of silicosis development and onset at different exposure durations (2 or 4 weeks) using various techniques such as histopathology, immunohistochemistry, Enzyme linked immunosorbent assay(ELISA),16â¯S rRNA, and untargeted metabolomics.These results indicate that exposure to silica leads to progressive damage to lung tissue with significant deterioration observed over time. Time-dependent cytokines such as the IL-4, IL-13, and IL-6 are detected in lung lavage fluid, the model group consistently exhibited elevated levels of these cytokines, indicating a persistent and worsening inflammatory response in the lungs. Meanwhile, HE and Masson results show that 4-week exposure to silica causes more obvious lung injury and pulmonary fibrosis. Besides, the model group consistently exhibited a distinct lung bacterial population, known as the Lachnospiraceae_NK4A136_group, regardless of exposure duration. However, with increasing exposure duration, specific temporal changes were observed in lung bacterial populations, including Haliangium, Allobaculum, and Sandaracinus (at 4 weeks; p < 0.05). Furthermore, our study revealed a strong correlation between the mechanism of silica-induced lung injury and three factors: oxidative stress, impaired lipid metabolism, and imbalanced amino acid metabolism. We observed a close correlation between cytokine levels, changes in lung microbiota, and metabolic disturbances during various exposure periods. These findings propose that a possible mechanism of silica-induced lung injury involves the interplay of cytokines, lung microbiota, and metabolites.
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Citocinas , Lesão Pulmonar , Pulmão , Microbiota , Dióxido de Silício , Dióxido de Silício/toxicidade , Animais , Pulmão/microbiologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Microbiota/efeitos dos fármacos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/microbiologia , Lesão Pulmonar/patologia , Citocinas/metabolismo , Masculino , Silicose/metabolismo , Líquido da Lavagem Broncoalveolar/químicaRESUMO
OBJECTIVES: To observe the CISD2 expression among PCOS patients and to explore its profound impact on the follicular microenvironment. Moreover, we want to elucidate the intricate mechanistic contribution of CISD2 to the onset and progression of PCOS. METHODS: Oxidase NOX2, mitophagy-related proteins, and CISD2 were detected by WB. The changes in mitochondrial structure and quantity were observed by transmission electron microscopy. Mitochondrial and lysosome colocalization was used to detect the changes of mitophagy. MDA kit, GSH and GSSG Assay kit and ROS probe were used to detect oxidative stress damage. RESULTS: We found that CISD2, mitophagy and oxidase in the GCs of PCOS patients were significantly increased. Testosterone stimulation leads to the increase of oxidase, mitophagy, and CISD2 in KGN cells. CISD2 inhibition promoted the increase of mitophagy, and the activation of mitochondria-lysosome binding, while alleviating the oxidative stress. CONCLUSIONS: Inhibition of CISD2 can improve the occurrence of oxidative stress by increasing the level of mitophagy, thus affecting the occurrence and development of PCOS diseases.
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Mitofagia , Estresse Oxidativo , Síndrome do Ovário Policístico , Adulto , Feminino , Humanos , Microambiente Celular/fisiologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Mitofagia/fisiologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologiaRESUMO
The Fufang Xueshuantong capsule (FXT) has significant preventive and therapeutic effects on diabetic retinopathy(DR), but the compatibility of its active components remains to be thoroughly explored. In this study, a zebrafish diabetic retinopathy model was established using high-mixed sugars, and the optimal ratios of notoginseng total saponins, total salvianolic acid, astragaloside, and harpagide were selected through orthogonal experiments. Furthermore, we used UPLC-QqQ/MS to detect the changes in amino acid content of DR zebrafish tissues after administration of FXT and its compatible formula to analyze the effects of FXT and its compatible formula on amino acid metabolites. The results showed that the final compatibility ratios of the components were 8: 5: 1: 6.6 by comprehensive evaluation of the indicators. FXT and its compatibility formula had beneficial effects on retinal vasodilatation, lipid accumulation in the liver, total glucose, and VEGF levels in DR zebrafish, and all of them could call back some amino acid levels in DR zebrafish. In this research, we determined the compatible formulation of the active ingredients in the FXT and investigated their efficacy in DR zebrafish for further clinical applications.
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Aminoácidos , Retinopatia Diabética , Medicamentos de Ervas Chinesas , Metabolômica , Peixe-Zebra , Animais , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Aminoácidos/metabolismo , Aminoácidos/análise , Cromatografia Líquida de Alta Pressão/métodos , Metaboloma/efeitos dos fármacosRESUMO
The modulation of microstructures in conjugated polymers represents a viable strategy for enhancing photocatalytic efficiency, albeit hampered by complex processing techniques. Here, we present an uncomplicated, template-free method to synthesize polymeric photocatalysts, namely BCN(x)@PPy, featuring a hollow nanotube-nanocluster core-shell superstructure. This configuration is realized through intramolecular covalent crosslinking and synergistic intermolecular donor-acceptor (D-A) interactions between phenylene pyrene (PPy, D) nanotubes and poly([1,1'-biphenyl]-3-carbonitrile) (PBCN, A) nanoclusters. Interestingly, the optimized BCN2@PPy composite demonstrates remarkably enhanced performance for photocatalytic hydrogen evolution, with an efficiency of 14.7-fold higher than that of unmodified PPy nanotubes. Experimental and density functional theory calculations revealed that BCN(x)@PPy composites are conducive to shortening photogenerated exciton migration, facilitating charge separation and transfer, reducing nanoclusters aggregation or re-stacking, and providing sufficient catalytically active sites, all contributing to the heightened efficiency in photocatalysis. These insights underscore the potential for precise molecular adjustments in conjugated polymers, advancing artificial photosynthesis.
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Purpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention. Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine-indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff's base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG. Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV-vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G-) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated. Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.
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Biofilmes , Verde de Indocianina , Raios Infravermelhos , Fotoquimioterapia , Terapia Fototérmica , Polietilenoglicóis , Biofilmes/efeitos dos fármacos , Fotoquimioterapia/métodos , Animais , Polietilenoglicóis/química , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Terapia Fototérmica/métodos , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Polietilenoimina/química , Polietilenoimina/farmacologia , Escherichia coli/efeitos dos fármacos , Óxido Nítrico , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Tamanho da PartículaRESUMO
Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.
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Linfócitos T CD8-Positivos , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Humanos , Feminino , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Receptores CXCR5/metabolismo , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Adulto , Pessoa de Meia-Idade , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunoglobulinas/metabolismo , Imunoglobulinas/imunologia , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologiaRESUMO
Twenty 3-acyloxymaltol/ethyl maltol derivatives (7a-j and 8a-j) were synthesized and evaluated in vitro for their anti-oomycete activity against Phytophthora capsici, respectively. Among all of twenty derivatives, more than half of the compounds 7f, 7h, 8a-h and 8j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 22.23 mg/L), and the EC50 values of 18.66, 20.32, 12.80, 16.18, 10.59, 14.98, 16.80, 10.36, 15.32, 12.64, and 13.59 mg/L, respectively. Especially, compounds 8c and 8f exhibited the best anti-oomycete activity against P. capsici with EC50 values of 10.59 and 10.36 mg/L, respectively. Overall, hydroxyl group of maltol/ethyl maltol is important active modification site.