RESUMO
Uveal melanoma (UM), the predominant primary ocular malignancy, often progresses to liver metastasis with limited therapeutic options. The interplay of the tumor microenvironment, encompassing secreted soluble factors, plays a crucial role in facilitating liver metastasis. In this study, the role is elucidated of the neural growth factor-inducible gene (VGF), a secreted neuropeptide precursor, in Gαq mutant UM. Employing a multiomics approach, encompassing transcriptomic and secretomic analyses, the intricate involvement of VGF in UM progression is unveiled. VGF is upregulated in Gαq mutant UM cells and associated with poor prognosis of UM patients. Targeting VGF significantly suppressed the growth of UM in vitro and in vivo. Further evidence shows that VGF is regulated by Gαq through MAPK/CREB pathway. Mechanistically, CREB modulates VGF expression by directly binding to consensus DNA response elements in the promoters of the VGF gene. Combined inhibition of Gαq and MEK remarkably reduces tumor burden in the UM xenograft model. Notably, VGF triggers liver metastatic colonization of UM and activates the fibrosis of hepatic stellate cells (HSCs), creating a favorable microenvironment, through an autocrine and paracrine loop. Furthermore, VGF directly binds to TGFBR2 and regulates TGF-ß-SMAD signaling pathway, thereby regulating genes associated with endothelial-mesenchymal transition (EMT) to promote metastasis. Taken together, these findings identify VGF as a pivotal driver in the progression and metastasis of Gαq mutant UM and confers a promising therapeutic target and strategy for UM patients.
RESUMO
OBJECTIVE: To investigate the current situation and influencing factors of postoperative nausea and vomiting (PONV) in lung cancer patients undergoing thoracoscopic surgery under general anesthesia, providing a reference for developing targeted PONV prevention and management strategies. METHODS: Using a consecutive sampling method, 200 lung cancer patients who underwent their first thoracoscopic surgery under general anesthesia between November 18, 2021, and March 1, 2022, at a tertiary class A cancer hospital in Liaoning Province, China, were selected. The occurrence of PONV within 24 h post-operation was assessed using WHO Postoperative Nausea and Vomiting Rating Criteria. Patient general information, surgical and medication data were systematically collected to analyze the independent influencing factors of PONV. RESULTS: Among the 200 patients undergoing thoracoscopic lung cancer surgery under general anesthesia, 75 (37.5%) experienced PONV. Logistic regression analysis indicated that being female, having a history of motion sickness, and a history of PONV were independent risk factors for the occurrence of PONV in these patients. Long-acting antiemetics such as penehyclidine hydrochloride and methylprednisolone were protective factors against PONV. CONCLUSION: The incidence of PONV in patients undergoing thoracoscopic lung cancer surgery under general anesthesia is relatively high. Nursing staff should focus on female patients and those with a history of motion sickness and PONV. Comprehensive preoperative assessments should be conducted, exploring multimodal analgesia and applying integrated prevention measures to reduce the occurrence of PONV and promote the rapid recovery of patients.
Assuntos
Anestesia Geral , Neoplasias Pulmonares , Náusea e Vômito Pós-Operatórios , Toracoscopia , Humanos , Feminino , Masculino , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Anestesia Geral/efeitos adversos , Idoso , Fatores de Risco , Toracoscopia/métodos , Incidência , China/epidemiologia , Antieméticos/uso terapêutico , AdultoRESUMO
Background and objectives: Exosomes, which are small nanoscale vesicles capable of secretion, have garnered significant attention in recent years because of their therapeutic potential, particularly in the context of kidney diseases. Notably, human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) are emerging as promising targeted therapies for renal conditions. The aim of this study was to investigate the therapeutic effects of hucMSC-Exos on diabetic kidney disease (DKD) both in vivo and in vitro. Additionally, this study seeks to elucidate cellular and molecular differentials, as well as the expression of relevant signaling pathways, through single-cell RNA sequencing. This endeavor was designed to enhance our understanding of the connection between hucMSC-Exos and the pathogenesis of DKD. Methods and results: The study commenced with the extraction and characterization of hucMSC-Exos, including the determination of their concentrations. Animal experiments were conducted to evaluate the therapeutic potential of hucMSC-Exos in a DKD mouse model. Subsequently, single-cell sequencing was employed to investigate the molecular mechanisms underlying the efficacy of extracellular vesicles in ameliorating DKD. These findings were further substantiated by cell-based experiments. Importantly, the results indicate that hucMSC-Exos can impede the progression of DKD in mice, with macrophage activation playing a pivotal role in this process. Conclusions: The in vivo experiments conclusively established hucMSC-Exos as a pivotal component in preserving renal function and retarding the progression of DKD. Our utilization of single-cell sequencing technology, in conjunction with in vivo and in vitro experiments, provides compelling evidence that M2 macrophages are instrumental in enhancing the amelioration of diabetic nephropathy.
RESUMO
Vanadium (V)-based oxides have garnered significant attention as cathode materials for aqueous zinc-ion batteries (AZIBs) due to their multiple valences and high theoretical capacity. However, their sluggish kinetics and low conductivity remain major obstacles to practical applications. In this study, Mo-doped V2O3 with oxygen vacancies (OVs, Mo-V2O3-x@NC) is prepared from a Mo-doped V-metal organic framework. Ex situ characterizations reveal that the cathode undergoes an irreversible phase transformation from Mo-V2O3-x to Mo-V2O5-x·nH2O and serves as an active material exhibiting excellent Zn2+ storage in subsequent charge-discharge cycles. Mo-doped helps to further improve cycling stability and increases with increasing content. More importantly, the synergistic effect of Mo-doped and OVs not only effectively reduces the Zn2+ migration energy barrier, but also enhances reaction kinetics, and electrochemical performance. Consequently, the cathode demonstrates ultrafast electrochemical kinetics, showing a superior rate performance (190.9 mAh g-1 at 20 A g-1) and excellent long-term cycling stability (147.9 mAh g-1 at 20 A g-1 after 10000 cycles). Furthermore, the assembled pouch cell exhibits excellent cycling stability (313.6 mAh g-1 at 1 A g-1 after 1000 cycles), indicating promising application prospects. This work presents an effective strategy for designing and fabricating metal and OVs co-doped cathodes for high-performance AZIBs.
RESUMO
The burdens of microbial food safety and environmental contamination make it necessary to search sustainable, safe, antibacterial and antioxidant active food packaging materials. This contribution proposed the use of copper-ferulic acid networks (CuFA NWs) as antibacterial substances. By immobilizing CuFA NWs into carrageenan matrix, a CuFA network-reinforced carrageenan-based packaging film (Carr/CuFA) was obtained via spontaneously hydrogen bond and electrostatic interaction indicated by ATR-IR and XPS. Interestingly, the addition of CuFA NWs increased the mechanical strength, surface hydrophobicity, and water vapor barrier properties of the carrageenan-based film, and imparted the film with UV-shielding capacity. Importantly, the Carr/CuFAx film exhibited effective antioxidant activity, and antibacterial performance against four foodborne bacteria. As a result, after confirming the safety of Carr/CuFA3 films by releasing, hemolysis and cell viability experiments, the Carr/CuFA3 film exhibited great potential in the safety control and preservation of fresh fruit by using blueberry and cherry as model fruit. In summary, this work provides a feasible candidate for the preservation and contamination control of fresh fruit.
Assuntos
Antibacterianos , Antioxidantes , Carragenina , Embalagem de Alimentos , Carragenina/química , Carragenina/farmacologia , Embalagem de Alimentos/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Antioxidantes/farmacologia , Antioxidantes/química , Cobre/química , Cobre/farmacologia , Fenóis/química , Fenóis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , VaporRESUMO
Intelligent indicator films with colorimetric pH indicator properties were developed, incorporating black soybean seed coat anthocyanin (BA), cellulose nanocrystals (CNC), and sodium alginate (SA) to monitor meat freshness. The effect of different CNC additions on the microstructure, water barrier properties of the films, and BA release kinetics were comprehensively investigated. The results showed that with the increasement of CNC addition, the mechanical properties of SA/BA/CNC films were improved, the water contact angle significantly increased from 51.6° to 69°. Moreover, water solubility, vapor adsorption, and permeability significantly decreased, indicating enhanced water barrier properties. The release kinetic results showed that BA was released rapidly within 72 h and slowly thereafter, and its release process was described by Fick's model. Films with 7 % and 10 % CNC had lower BA diffusion coefficients. Their diffusions were formulated as linear regression equations (y = nx + a), where R2 was >0.80 and n was <0.50. Structural characterization showed that CNC immobilized BA mainly through hydrogen bonding, forming compact network microstructures with SA and BA. Meat freshness monitoring results showed that the film containing 7 % CNC showed visible color changes with increasing total volatile basic nitrogen and pH, along with low BA release, high water barrier and mechanical properties. Therefore, CNC has great potential for improving the physicochemical properties of indicator films, and the intelligent colorimetric indicator film could be applied to various food product.
Assuntos
Alginatos , Antocianinas , Celulose , Embalagem de Alimentos , Carne , Nanopartículas , Alginatos/química , Celulose/química , Nanopartículas/química , Antocianinas/química , Carne/análise , Embalagem de Alimentos/métodos , Concentração de Íons de Hidrogênio , Água/química , Fenômenos Químicos , Solubilidade , Permeabilidade , CinéticaRESUMO
The purpose of this study was to clarify effects of water changes on the quality and volatile compounds of Penaeus monodon during frozen storage. The content of immobilized water decreased significantly while the bound water and free water increased significantly. Total sulfhydryl content, and Ca2+-ATPase activity decreased significantly to 68.31 µmol/g and 0.127 U/mg, meantime, carbonyl content and MFI value increased significantly to 2.04 µmol/g prot and 55.10. Total of 50 volatile compounds were identified. Nonanal (M & D), 2-nonanone and octanal were only detected in fresh samples, while 3-hydroxy-2-butanone and 1-hydroxy-2-propanone were only found in the samples after 20 days of storage. Correlation analysis revealed that 6 of the volatile compounds were associated with the change of free water. Total of 28 and 17 volatile compounds showed significant correlations with the immobilized water and bound water, respectively. Four volatile compounds have the potential to be used as the flavor marker.
Assuntos
Congelamento , Penaeidae , Compostos Orgânicos Voláteis , Água , Animais , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Água/análise , Água/química , Penaeidae/química , Penaeidae/metabolismo , Armazenamento de AlimentosRESUMO
Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.
Assuntos
Antibacterianos , Antioxidantes , Cobre , Conservação de Alimentos , Ovalbumina , Superóxido Dismutase , Ovalbumina/química , Cobre/química , Cobre/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Superóxido Dismutase/metabolismo , Superóxido Dismutase/química , Antibacterianos/farmacologia , Antibacterianos/química , Conservação de Alimentos/métodos , Espécies Reativas de Oxigênio/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologiaRESUMO
Naturally sourced pH-sensitive indicator films are of interest for real-time monitoring of food freshness through color changes because of their safety. Therefore, natural pigments for indicator films are required. However, pigment stability is affected by environmental factors, which can in turn affect the sensitivity and color stability of the pH-sensitive indicator film. First, natural pigments (anthocyanin, betalain, curcumin, alizarin, and shikonin) commonly used in pH-sensitive indicator films are presented. Subsequently, the mechanisms behind the change in pigment color under different pH environments and their applications in monitoring food freshness are also described. Third, influence factors, such as the sources, types, and pH sensitivity of pigments, as well as environmental parameters (light, temperature, humidity, and oxygen) of sensitivity and color stability, are analyzed. Finally, methods for improving the pH-sensitive indicator film are explored, encapsulation of natural pigments, incorporation of a hydrophobic film-forming matrix or function material, and protective layer have been shown to enhance the color stability of indicator films, the addition of copigments or mental ions, blending of different natural pigments, and the utilization of electrospinning have been proved to increase the color sensitivity of indicator films. This review could provide theoretical support for the development of naturally sourced pH-sensitive indicator films with high stability and sensitivity and facilitate the development in the field of monitoring food freshness.
Assuntos
Cor , Embalagem de Alimentos , Concentração de Íons de Hidrogênio , Embalagem de Alimentos/métodos , Pigmentos Biológicos/químicaRESUMO
Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.
RESUMO
Common epidermal growth factor receptor (EGFR) mutations are usually not considered for immunotherapy in non-small cell lung cancer (NSCLC) due to poor efficacy. However, whether uncommon EGFR mutations are suitable for immunotherapy has not been thoroughly studied. Thus, we explored the tumor immune microenvironment (TME) features in uncommon EGFR mutant NSCLC. In this study, a total of 41 patients with EGFR mutations were included, the majority (85.4%) of whom were stage I. Among them, 22 patients harbored common mutations, while 19 patients presented with uncommon mutations. Compared with common mutations, uncommon mutations exhibited more infiltrating T cells and fewer M2 macrophages, upregulated expression of antigen processing and a presentation pathway. Unsupervised clustering based on the mIF profile identified two classes with heterogeneous TME in uncommon mutations. Class 1 featured the absence of PD-1+ cytotoxic T cell infiltration, and class 2 displayed a hotter TME because of the downregulated expression of hypoxia (p < 0.001), oxidative phosphorylation (p = 0.009), and transforming growth factor beta signaling (p = 0.01) pathways as well as increased expression of CTLA4 (p = 0.001) and PDCD1 (p = 0.004). The association of CTLA4 and PDCD1 with TME profiles was validated in a TCGA lung adenocarcinoma cohort with uncommon EGFR mutations. Our study reveals the distinct and heterogeneous TME features in uncommon EGFR mutant NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Mutação , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Oxirredutases Intramoleculares/genética , Fatores Inibidores da Migração de Macrófagos/genética , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Antígeno CTLA-4/genética , Antígeno CTLA-4/metabolismo , Adulto , Idoso de 80 Anos ou maisRESUMO
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the disruption of synaptic communication among millions of neurons. Recent research has highlighted the potential therapeutic effectiveness of natural polyphenolic compounds in addressing AD. Soybeans are abundant in polyphenols, and their polyphenolic composition undergoes significant alteration through fermentation by Eurotium cristatum. Through comprehensive database searches, we identified active components within fermented soybean polyphenols and genes associated with AD. Subsequently, we utilized Venn diagrams to analyze the overlap between AD-related genes and these components. Furthermore, we visualized the network between intersecting targets and proteins using Cytoscape software. The anti-AD effects of soybeans were further explored through comprehensive analysis, including protein-protein interaction analysis, pathway enrichment analysis, and molecular docking studies. Our investigation unveiled 6-hydroxydaidzein as a major component of fermented soybean polyphenols, shedding light on its potential therapeutic significance in combating AD. The intersection between target proteins of fermented soybeans and disease-related targets in AD comprised 34 genes. Protein-protein interaction analysis highlighted key potential targets, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycogen synthase kinase 3 beta (GSK3B), amyloid precursor protein (APP), cyclin-dependent kinase 5 (CDK5), and beta-site APP cleaving enzyme 1 (BACE1). Molecular docking results demonstrated a robust binding effect between major components from fermented soybeans and the aforesaid key targets implicated in AD treatment. These findings suggest that fermented soybeans demonstrate a degree of efficacy and present promising prospects in the prevention of AD.
Assuntos
Doença de Alzheimer , Fermentação , Glycine max , Simulação de Acoplamento Molecular , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Glycine max/química , Humanos , Farmacologia em Rede , Mapas de Interação de Proteínas/efeitos dos fármacos , Polifenóis/farmacologia , Polifenóis/química , Isoflavonas/farmacologia , Isoflavonas/química , Isoflavonas/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
BACKGROUND: The standard care for resectable non-small cell lung cancer (NSCLC) involves perioperative therapy combining chemotherapy and immune checkpoint inhibitors, typically lasting 6 to 12 months. However, the optimal treatment strategies for potentially resectable squamous cell lung carcinoma (SCC) remain unclear. This Phase 2 trial aimed to assess the efficacy and safety of a condensed four-cycle perioperative treatment regimen with tislelizumab combined with chemotherapy in patients with potentially resectable stage III SCC. METHODS: Patients with potentially resectable stage IIIA-IIIB (N2) SCC received intravenous tislelizumab, albumin-bound paclitaxel, and carboplatin for up to four cycles. The primary endpoints were major pathologic response (MPR) and incidence of treatment-related adverse events. Safety and potential biomarkers for efficacy prediction were also assessed. RESULTS: Among 35 enrolled patients, 32 underwent surgery with R0 resection achieved in all cases. MPR was achieved in 24 patients and pathological complete response (pCR) in 14 patients. Radiographic objective response was observed in 31 patients. The 12-month and 24-month event-free survival rate was 85.7 and 61.0%, respectively. Four patients experienced grade 3 or 4 adverse events. Tumor tissue based next-generation sequencing revealed the potential associations between several biomarkers and pathological response, including tumor neoantigen burden score, 18-gene expression profile score, CD8 + T cells, M1/M2 macrophages ratio and interferon-gamma expression level. Besides, circulating tumor DNA (ctDNA) dynamics and concentration were also associated with pathological response and the presence of ctDNA at postoperative month 1 was a strong predictor for disease relapse. Furthermore, metagenomic sequencing in bronchoalveolar lavage fluid demonstrated Streptococcus was the most abundant genus in the pCR group. CONCLUSIONS: A condensed four-cycle perioperative treatment regimen of tislelizumab combined with chemotherapy demonstrated promising efficacy and manageable toxicities in potentially resectable stage III SCC. Specific biomarkers showed potential for predicting treatment efficacy and the mechanism of superior antitumor response of pCR patients was preliminarily and indirectly explored. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05024266. Registered August 27, 2021.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Estadiamento de Neoplasias , Assistência Perioperatória/métodos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Resultado do Tratamento , Adulto , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologiaRESUMO
Most phenolic compounds in beans exist in complex, insoluble binding forms that bind to cell wall components via ether, ester, or glucoside bonds. In the process of solid-state fermentation, Eurotium Cristatum can produce many hydrolase enzymes, such as α-amylase, pectinase, cellulase and ß-glucosidase, which can effectively hydrolyze ether, ester or glucoside bond, release bound polyphenols, and increase polyphenol content in soybeans. When the fermentation conditions of soybean were fermentation time 12 days, inoculation amount 15% and initial pH 2, the content of free polyphenols in fermented soybean was 2.79 mg GAE/g d.w, which was 4.98 times that of unfermented soybean. The contents of bound polyphenols and total phenols in fermented soybean were 0.62 mg GAE/g d.w and 3.41 mg GAE/g d.w, respectively, which were 2.38 times and 4.16 times of those in unfermented soybean. At the same time, the inhibitory effect of free polyphenols in fermented soybean on acetylcholinesterase reached 91.51%. Thus, our results demonstrated that solid state fermentation and Eurotium Cristatum can be used as an effective way to increase soybean polyphenol content and combat Alzheimer's disease.
RESUMO
Clinical therapy for widespread infections caused by Streptococcus pneumoniae (S. pneumoniae), such as community-acquired pneumonia, is highly challenging. As an important bacterial toxin, hydrogen peroxide (H2O2) secreted by S. pneumoniae can suppress the host's immune system and cause more severe disease. To address this problem, a hyaluronic acid (HA)-coated inorganic catalase-driven Janus nanomotor was developed, which can cleverly utilize and decompose H2O2 to reduce the burden of bacterial infection, and have excellent drug loading capacity. HA coating prevents rapid leakage of loaded antibiotics and improves the biocompatibility of the nanomaterials. The Janus nanomotor converted H2O2 into oxygen (O2), gave itself the capacity to move actively, and encouraged widespread dispersion in the lesion site. Encouragingly, animal experiments demonstrated that the capability of the nanomotors to degrade H2O2 contributes to diminishing the proliferation of S. pneumoniae and lung tissue damage. This self-propelled drug delivery platform provides a new therapeutic strategy for infections with toxin-secreting bacteria.
Assuntos
Catalase , Ácido Hialurônico , Peróxido de Hidrogênio , Streptococcus pneumoniae , Ácido Hialurônico/química , Catalase/metabolismo , Catalase/química , Streptococcus pneumoniae/efeitos dos fármacos , Animais , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Nanoestruturas/química , Humanos , Pneumonia/tratamento farmacológicoRESUMO
The emergence of flexible fabric-based pneumatic actuators (FPAs) with pre-programmable motion capabilities, enhanced security and versatile interaction features significantly advances the construction of sophisticated soft robotic systems, owing to their enhanced security and versatile interaction features. Despite these promising attributes, the commercial viability of FPA products faces a considerable amount of challenges, primarily stemming from the scarcity of highly deformable fabric structures and the availability of industrial fabrication approaches. Taking inspiration from the anisotropic nature of lobster antennae, we propose a scalable and economical strategy to fabricate functional FPAs using nonwoven fabric material with superior mechanical anisotropy. This innovative method involves the adoption of tunable inelastic constrained wires sewn onto extensible nonwoven fabrics with regular wrinkles. This nonwoven fabric-based pneumatic actuator (NFPA) demonstrates specific motion profiles with curvature of over 0.6 cm-1 and output forces of over 140 cN under adjustable pressure conditions. Guided by the constrained wire combinations, NFPA enables diverse programmable motions like spiraling, assistance, and grasping. Furthermore, NFPA incorporated with specific sensors exhibits significant potential in wearable devices with real-time environmental detection for rehabilitation applications. Our work contributes a distinctive insight into the design of programmable NFPAs and enlightens an arena toward versatile soft robotic applications.
RESUMO
Electrolytes with anion-dominated solvation are promising candidates to achieve dendrite-free and high-voltage potassium metal batteries. However, it's challenging to form anion-reinforced solvates at low salt concentrations. Herein, we construct an anion-reinforced solvation structure at a moderate concentration of 1.5â M with weakly coordinated cosolvent ethylene glycol dibutyl ether. The unique solvation structure accelerates the desolvation of K+, strengthens the oxidative stability to 4.94â V and facilitates the formation of inorganic-rich and stable electrode-electrolyte interface. These enable stable plating/stripping of K metal anode over 2200â h, high capacity retention of 83.0 % after 150 cycles with a high cut-off voltage of 4.5â V in K0.67MnO2//K cells, and even 91.5 % after 30 cycles under 4.7â V. This work provides insight into weakly coordinated cosolvent and opens new avenues for designing ether-based high-voltage electrolytes.
RESUMO
Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.
Assuntos
Glucose Oxidase , Hiperglicemia , Óxido Nítrico , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico/metabolismo , Animais , Glucose Oxidase/metabolismo , Humanos , Camundongos , Glucose/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
As an iron dependent regulatory cell death process driven by excessive lipid peroxides (LPO), ferroptosis is recognized as a powerful weapon for pancreatic cancer (PC) therapy. However, the tumor microenvironment (TME) with hypoxia and elevated glutathione (GSH) expression not only inhibits LPO production, but also induces glutathione peroxidase 4 (GPX4) mediated LPO clearance, which greatly compromise the therapeutic outcomes of ferroptosis. To address these issues, herein, a novel triple-enhanced ferroptosis amplifier (denoted as Zal@HM-PTBC) is rationally designed. After intravenous injection, the overexpressed H2O2/GSH in TME induces the collapse of Zal@HM-PTBC and triggers the production of oxygen and reactive oxygen species (ROS), which synergistically amplify the degree of lipid peroxidation (broaden sources). Concurrently, GSH consumption because of the degradation of the hollow manganese dioxide (HM) significantly weakens the activity of GPX4, resulting in a decrease in LPO clearance (reduce expenditure). Moreover, the loading and site-directed release of zalcitabine further promotes autophagy-dependent LPO accumulation (enhance effectiveness). Both in vitro and in vivo results validated that the ferroptosis amplifier demonstrated superior specificity and favorable therapeutic responses. Overall, this triple-enhanced LPO accumulation strategy demonstrates the ability to facilitate the efficacy of ferroptosis, injecting vigorous vitality into the treatment of PC.
Assuntos
Ferroptose , Glutationa , Peróxidos Lipídicos , Neoplasias Pancreáticas , Ferroptose/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Animais , Peróxidos Lipídicos/metabolismo , Humanos , Linhagem Celular Tumoral , Glutationa/metabolismo , Camundongos , Compostos de Manganês/química , Óxidos/química , Espécies Reativas de Oxigênio/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos Nus , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos BALB CRESUMO
Organic materials have attracted extensive attention for potassium-ion batteries due to their flexible structure designability and environmental friendliness. However, organic materials generally suffer from unavoidable dissolution in aprotic electrolytes, causing an unsatisfactory electrochemical performance. Herein, we designed a weakly solvating electrolyte to boost the potassium storage performance of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). The electrolyte induces an in situ morphology evolution and achieves a nanowire structure. The weakly dissolving capability of ethylene glycol diethyl ether-based electrolyte and unique nanowire structure effectively avoid the dissolution of PTCDA. As a result, PTCDA shows excellent cycling stability (a capacity retention of 89.1% after 2000 cycles) and good rate performance (70.3 mAh g-1 at 50C). In addition, experimental detail discloses that the sulfonyl group plays a key role in inducing morphology evolution during the charge/discharge process. This work opens up new opportunities in electrolyte design for organic electrodes and illuminates further developments of potassium-ion batteries.