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A large and growing body of literature has investigated the broad antibacterial spectrum and strong synergistic antimicrobial activity of medium chain monoglycerides (MCMs) have been widely investigated. Recently, more and more researches have focused on the regulation of MCMs on metabolic health and gut microbiota both in vivo and in vitro. The current review summarizes the digestion, absorption and metabolism of MCMs. Subsequently, it focuses on the functional and nutritional properties of MCMs, including the antibacterial and antiviral characteristics, the modulation of metabolic balance, the regulation of gut microbiota, and the improvement in intestinal health. Additionally, we discuss the most recent developments and application of MCMs using nanotechnologies in food industry, poultry and pharmaceutical industry. Additionally, we analyze recent application examples of MCMs and their nanotechnology formation used in food. The development of nanotechnology platforms facilitating molecular encapsulation and functional presentation contribute to the application of hydrophobic fatty acids and monoglycerides in food preservation and their antibacterial effectiveness. This study emphasizes the metabolic mechanisms and biological activity of MCMs by summarizing the prevailing state of knowledge on this topic, as well as providing insights into prospective techniques for developing the beneficial applications of MCMs to realize the industrialized production.
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Particulate matter (PM10) changes have been confirmed as one of the contributory factors affecting human health, the association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease (COPD) with comorbidity diseases was rarely reported. The same inpatient more than twice times admissions with COPD illness from January 1, 2016 to December 31, 2021 were identified from hospitals in the 17 cities of Henan, Central China. City-specific associations were firstly estimated using the case time series (CTS) model and then combined to obtain the regional average association. The multivariate meta-analytic model produces pooled estimates of the set of coefficients representing the PM10-COPD hospitalizations association across the 17 cities. Cause-specific hospitalization analyses were performed by COPD patients with different comorbidity combinations. A total of 34,348 elderly (age ≥ 65) subjects were analyzed and with a total of 35,122.35 person-years. These coefficients can be used to compute the linear exposure-response curve expressed as relative risk (RR) in per 10 µg/m3 increase in PM10 at lag03, which was 1.0091 (95% CI 1.0070-1.0112) for COPD with comorbidity, 1.0089 (95% CI 1.0067-1.0110) for COPD with circulatory system diseases, 1.0079 (95% CI 1.0052-1.0105) for COPD with respiratory system diseases, 1.0076 (95% CI 1.0032-1.0121) for COPD with endocrine system diseases, and 1.0087 (95% CI 1.0013-1.0162) for COPD with genitourinary system diseases, respectively. Some heterogeneity was found across cities, with estimates ranging from 1.0227 in the Puyang and Jiaozuo to 1.0053 in Henan Provance, China. The effect of higher PM10, on average, was higher in studies for northern cities, with a steeper raise in risk: per 10 µg/m3 increase in PM10, the RR from 1.0062 (95% CI 1.0030-1.0093) for the 10th percentile of latitude to 1.0124 (95% CI 1.0089-1.0160) for the 90th percentile. Our findings indicated that PM10 exposure may increase the risk of hospitalizations for COPD with comorbidity. Moreover, there might be a higher morbidity risk associated with PM10 in northern latitudes, indicating that stricter air quality standards could potentially reduce PM10-related morbidity among individuals with COPD. These findings have implications for the implementation of effective clean air interventions aligned with national climate policies.
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Poluentes Atmosféricos , Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Poluentes Atmosféricos/análise , Cidades/epidemiologia , Poluição do Ar/análise , Material Particulado/análise , Hospitalização , Doença Pulmonar Obstrutiva Crônica/epidemiologia , China/epidemiologia , Comorbidade , Exposição Ambiental/análiseRESUMO
Metalenses have been widely investigated for their features of high design freedom. For practical applications, it is necessary to maximize the efficiency of the metalens. However, it is a great challenge to realize both a high numerical aperture (NA) and high-efficiency metalens in the community. Here, we introduce a method to design a hybrid metalens with a large numerical aperture and high focusing efficiency at terahertz frequency. The hybrid metalens consists of gradient metasurfaces in the central area and metagrating in the peripheral area to achieve high-efficiency beam focusing. To verify this concept, a hybrid metalens with a numerical aperture of 0.95 was designed at λ = 118.8â µm. The simulation results demonstrate that the focusing efficiency of the hybrid metalens is 65.8%. The experimental results show that the designed metalens is able to increase the focusing efficiency from 22.8% to 41.7%. The full widths at half maxima (FWHMs) of the focused spots of the hybrid metalens in the x direction and y direction are 0.72λ and 0.45λ, respectively. The proposed high-efficiency hybrid metalens has promising application prospects in various applications of a complex optical system.
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Soft silicone has been widely used for anti-icing coating, but the ice adhesion strength is usually scaled with the iced area at a relatively large thickness. On the other hand, a thin rigid poly(vinyl chloride) (PVC) film could be independent of the iced area and was named a low-interfacial-toughness material. Thus, a soft and rigid integrated (SRI) coating was prepared by doping PVC particles into a silicone matrix here. The introduction of PVC particles not only served as phase II to accelerate the stress concentration but also favored the formation of a wrinkle structure. After further introducing plasticizers, this SRI coating not only has a very low ice adhesion strength at a low iced length but also tends to a limit value irrespective of the iced length, which further leads to excellent large-area deicing behavior. Furthermore, the SRI coating demonstrated outstanding chemical stability, mechanical robustness, and on-field repairability.
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Two-dimensional (2D) Janus materials exhibit an outstanding potential that can meet the rigorous requirements of photocatalytic water splitting resulting from their unique atomic arrangement. However, these materials are quite scarce. Through ab initio density functional theory calculations, we introduce a kagome topology into the honeycomb lattice of blue phosphorene using phosphorus and bismuth atoms to build a hybrid honeycomb-like kagome lattice, realized by a hitherto unknown kagome-like Janus-like BiP3 monolayer with robust stability. Excitingly, the out-of-plane asymmetry benefiting from kagome and honeycomb topologies gives rise to a significantly negative out-of-plane Poisson's ratio and an obvious built-in electric field pointing from the sublayer of the P atom to the sublayer of the Bi atom. In conjunction with the investigations that encompass semiconducting properties, such as a quasi-direct gap, suitable band-edge positions, effective visible-light absorption, and high carrier mobility, the BiP3 monolayer achieves overall water splitting at pH 0-14 regardless of strain. Moreover, this intrinsic electric field provides a sufficient photogenerated carrier driving force for water splitting. The bare BiP3 comprises P and Bi atoms that function as catalysts for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) active sites, respectively. Upon exposure to light, the reaction of water into H2 and O2 can be observed across a pH range of 0-14. Meanwhile, by designing a transition-metal single-atom catalyst (TM@BiP3), our investigations have shown that embedding a single TM on BiP3 is a feasible route to improving the HER/OER activity by reducing the overpotentials to -0.039 and 0.58 eV for Mo and Os atoms, respectively. In this case, the positive value of the external potential acts as a sufficient OER driving force, i.e., in the light environment, the Os@BiP3 system can promote water molecules spontaneously oxidized into O2 at pH 0-14.
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BACKGROUND: This study aimed to examine the bidirectional relationship between social isolation and cognitive performance among Chinese middle-aged and older adults. METHODS: We used four waves of data from the China Health and Retirement Longitudinal Study. A latent growth model (LGM) was applied to examine the association between social isolation and cognitive performance across different characteristics. RESULTS: In the analysis, we ultimately included 9,367 participants after excluding respondents with missing key variables. Social isolation and cognitive performance showed significant differences across time. After adjusting for the confounders, there was a significant association between higher social isolation and poor cognitive performance (ß = -1.38, p < 0.001), and higher levels of social isolation resulted in a more pronounced decline in cognition over time (ß = 0.17, p < 0.001). Additionally, the path coefficient between the initial level of cognition at baseline and the slope of social isolation was - 0.07 (p < 0.001) and 0.01 (p = 0.021), respectively. For the correlation between slopes, our study found that females' cognition scores were more susceptible to social isolation (ß = - 2.78, p < 0.001). Similarly, regarding cognition scores, the influence of social isolation was greater among people with education below the primary level (ß = - 2.89, p = 0.002) or a greater number of chronic diseases (ß = - 2.56, p = 0.001). CONCLUSION: Our findings support the bidirectional association between social isolation and cognition. Specifically, higher baseline social isolation and its rate of increase over time contribute to an intensification of cognitive decline at follow-up. Besides, poorer cognitive performance predicted higher social isolation.
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Cognição , Disfunção Cognitiva , Isolamento Social , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Povo Asiático , Estudos Longitudinais , ChinaRESUMO
The roles of medium- and long-chain triacylglycerols (MLCT) on health benefits under high fat diet (HFD) conditions remain in dispute. This study was conducted to investigate the effects of novel LaPLa-rich MLCT on the glycolipid metabolism and gut microbiota in HFD-fed mice when pork fat is half replaced with MLCT and palm stearin (PS). The results showed that although MLCT could increase the body weight in the mouse model, it can improve the energy utilization, regulate the glucose and lipid metabolism, and inhibit the occurrence of inflammation. Furthermore, 16S rRNA gene sequencing of gut microbiota indicated that PS and MLCT affected the overall structure of the gut microbiota to a varying extent and specifically changed the abundance of some operational taxonomic units (OTUs). Moreover, several OTUs belonging to the genera Dorea, Streptococcus, and g_Eryipelotrichaceae had a high correlation with obesity and obesity-related metabolic disorders of the host. Therefore, it can be seen that this new MLCT has different properties and functions from the previous traditional MLCT, and it can better combine the advantages of MLCT, lauric acid, and sn-2 palmitate, as well as the advantages of health function and metabolism. In summary, this study explored the effects of LaPLa-enriched lipids on glycolipid metabolism in mice, providing theoretical support for future studies on the efficacy of different types of conjugated lipids, intending to apply them to industrial production and subsequent development of related products.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Peso Corporal , Obesidade/etiologia , Obesidade/metabolismo , Triglicerídeos/química , Metabolismo dos Lipídeos , Glicolipídeos/farmacologiaRESUMO
Photothermal therapy (PTT) is a promising treatment that efficiently suppresses local cancer, but fails to induce a robust antitumor immune response against tumor metastasis and recurrence. In this study, a NIR responsive nano-immunostimulant (Mn/A-HP NI) is fabricated by entrapping manganese and azo-initiator (AIPH) into hyaluronic acid-based polypyrrole nanoparticle. The as-prepared Mn/A-HP NIs with a high photothermal conversion efficiencey of 20.17% dramatically induced the imunogenic cell death of tumor cells and triggered the release ATP and HMGB1. Meanwhile, the hyperthermia induced AIPH decomposition to produce alkyl radicals which further destroyed cancer cells. Furthermore, the Mn/A-HP NIs were capable of promoting the maturation and antigen cross-presentation ability of dendritic cells. Consequently, the multifunctional Mn/A-HP NIs provided a combined treatment via integrating PTT/chemo-dynamic therapy and immune activation for tumor therapy.
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Hipertermia Induzida , Nanopartículas , Polímeros/química , Terapia Fototérmica , Pirróis/farmacologia , Nanopartículas/química , Linhagem Celular Tumoral , FototerapiaRESUMO
BACKGROUND: Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π-π stacking interactions. RESULTS: The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo. CONCLUSIONS: This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.
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Nanopartículas , Neoplasias , Humanos , Azul de Metileno/farmacologia , Nanopartículas/uso terapêutico , Neoplasias/terapia , Ovalbumina , Fototerapia/métodos , Polímeros/farmacologia , Pirróis/farmacologiaRESUMO
Plasmonic lithography can utilize evanescent waves to produce subdiffraction patterns. However, the high loss and shallow depth of patterns severely obstruct its application in practice. In this work, a large focal depth is achieved for deep subwavelength lithography. It is accomplished by employing radially polarized light to excite surface plasmons on a concentric annular grating and combining designed epsilon-near-zero metamaterial to select a high spatial frequency mode, which can shape an evanescent Bessel beam in a photoresist (PR). Moreover, the intensity distribution of the subdiffraction beam can be further enhanced and uniformized by adding reflective layers. It is shown that a needle-like beam with a focal depth of over 500 nm (1.23λ) is formed in the PR layer, and the full width at half maximum of the beam is widened from only 80 nm (0.2λ) to 94 nm (0.23λ). The analyses indicate that this design is applicable for direct writing lithography to produce super-resolution patterns with small feature size, high aspect ratio, and strong field intensity.
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The terahertz (THz) lens is an essential and strategic element of THz optical systems, while a conventional THz lens cannot even reach high resolution due to the diffraction limit. Optical super-oscillation paves a way to generate sub-diffraction hotspots in the far field, and demonstrates the capacity for resolution improvement of microscopic imaging in the visible range. However, there are few demonstrations of THz lenses for focusing hotspots or needles based on super-oscillation. We propose and experimentally demonstrate a far-field sub-diffraction focusing planar lens, consisting of a sub-wavelength concentric ring structure array, for a wavelength of 118.8 µm with focal length 420λ and radius 160λ. Utilizing the silicon-etching process, a sub-diffraction focusing lens is fabricated. The experimental results show that the planar lens can generate a sub-diffraction needle with length 19.7λ in the focal region along the optic axis. Moreover, the smallest focal spot, with a transverse size of 1.212λ, is smaller than the diffraction limit of 1.476λ. The proposed sub-diffraction optical needle planar lens can substitute for its traditional counterpart, and it has great potential in super-resolution tomography THz imaging systems.
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OBJECTIVES: To investigate the feasibility of using human-specific insulin radioimmunoassay (Ins-RIA) kit to measure the concentrations of serum insulin in minipigs. METHODS: The Serum samples (219) of Bama minipigs were collected. The concentrations of serum insulin in Bama minipigs were measured by Ins-RIA kit and porcine-specific insulin enzyme linked immunosorbent assay (Ins-ELISA) kit, respectively. The linear regression analysis was undertaken in a randomly selected 175 samples (80% of total samples) to establish predictive equations between the concentrations of serum insulin measured by Ins-ELISA and the concentrations of serum insulin measured by Ins-RIA. The equations were then cross-validated in the remaining 44 samples (20% of total samples) that had not been included in the regression analysis. RESULTS: Measured insulin concentration was lower with the Ins-ELISA than that with the Ins-RIA [(15.32±15.50) µIU/mL vs. (32.31±21.74) µIU/mL, respectively, P<0.000 1]; The final predictive equation for the Ins-ELISA (µIU/mL) was equal to -7.29+0.70 × Ins-RIA(µIU/mL) ( R2=0.94). The differences between the predicted values and the actual measured values were 17.18%. CONCLUSIONS: Insulin values in Bama minipigs obtained from the Ins-ELISA and Ins-RIA are not equivalent and differ significantly. However, the insulin concentration by Ins-ELISA can be well estimated by Ins-RIA.
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Insulina/sangue , Radioimunoensaio , Animais , Ensaio de Imunoadsorção Enzimática , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Suínos , Porco MiniaturaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss. The main pathological features are neuronal fibrillary tangles caused by amyloid beta deposition and hyperphosphorylation of tau protein, accompanied by neuronal death and loss of synaptic structure. Early diagnosis is the key to the treatment of AD. It is known that some small molecular components are related to the pathogenesis of AD. This article will summarize the common AD biomarkers in cerebrospinal fluid and blood and analyze the current status of AD biomarkers and future research directions. This review summarizes the promising biomarkers for the diagnosis of AD in the last decade and describes their changes in AD body fluids. The diagnostic biomarkers related to AD were mainly distributed in cerebrospinal fluid and blood. Significant changes in these molecules can be detected in cerebrospinal fluid and blood, and they are correlated with AD severity. These humoral molecules have necessary relationship with AD and can be used as AD biomarkers to assist early diagnosis of AD.
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Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Humanos , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Precoce , Proteínas tau/líquido cefalorraquidiano , Proteínas tau/sangue , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidianoRESUMO
Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.
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Quitosana , Infecções Estafilocócicas , Infecção dos Ferimentos , Animais , Camundongos , Antioxidantes/farmacologia , Hidrogéis/farmacologia , Escherichia coli , Staphylococcus aureus , Extratos Vegetais/farmacologia , Cicatrização , Antibacterianos/farmacologiaRESUMO
Bacterial infections are a serious threat to wound healing and skin regeneration. In recent years, photothermal therapy (PTT) has become one of the most promising tools in the treatment of infectious diseases. However, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of photosensitizers or photothermal agents. Therefore, how to improve the therapeutic efficiency and biosafety from material design is still a major challenge at present. In this study, the carboxymethyl chitosan (CMCS) and protocatechuic aldehyde (PA) hydrogels based on horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) enzymatic catalysis was developed. Therein, HRP and H2O2 catalyzed cross-linking while polymerizing PA, which not only endowed the hydrogels with photothermal responsiveness but also with good biosafety through this enzyme-catalyzed green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared (NIR). Moreover, the ultra-rapid gelation, strong tissue adhesion, high swelling ability, good antioxidant property and hemostatic property of the CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis were suitable for the treatment of skin wounds. Meanwhile, NIR-assistant CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis reduced inflammation, decreased bacterial infection, and promoted collagen deposition and angiogenesis, which showed remarkable therapeutic effects in a skin wound infection model. All results indicate that this green approach to introduce photothermal property by HRP-catalyzed PA polymerization endows the hydrogels with efficient photothermal conversion efficiency, suggesting that they are promising to provide new options for replacing photothermal agents and photosensitizers. STATEMENT OF SIGNIFICANCE: In recent years, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of agent photosensitizers or photothermal agents. In this study, the carboxymethyl chitosan and protocatechuic aldehyde hydrogels based on horseradish peroxidase and hydrogen peroxide enzymatic catalysis was developed. The photothermal properties of hydrogels were transformed from absent to present just by horseradish peroxidase-catalyzed protocatechuic aldehyde polymerization in a green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared. The green approach of introducing photothermal properties from material design solves the biosafety challenge. Therefore, this study is expected to provide new options for alternative photothermal agents and photosensitizers.
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Antibacterianos , Antioxidantes , Quitosana , Hidrogéis , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Quitosana/química , Quitosana/farmacologia , Quitosana/análogos & derivados , Peróxido de Hidrogênio , Química Verde , Pele/patologia , Pele/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Camundongos , Peroxidase do Rábano Silvestre/química , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/microbiologiaRESUMO
Platelet-rich plasma (PRP) contains a variety of growth factors (GFs) and has been used in the treatment of a variety of diseases, including skin lesions. In particular, PRP with low immunogenicity will be more widely used. However, the explosive release of GFs limits its further application. In order to achieve controlled release of GFs, a multifunctional and reactive oxygen species (ROS)/pH dual responsive hydrogel was developed to load PRP derived from human cord blood for the treatment of skin wound healing. Based on the hydrogen bond and Schiff base interaction, carboxymethyl chitosan (CMCS), oxidized dextran (Odex) and oligomeric procyanidins (OPC) were crosslinked to form CMCS/Odex/OPC/PRP hydrogel with good injectability, self-healing, adhesion, ROS scavenging, antibacterial activity, controlled and sustained release of GFs. In vitro cell experiments suggested that this hydrogel possessed excellent biocompatibility and could promote the proliferation and migration of L929. In vivo healing of full-layer skin wounds further indicated that the prepared hydrogel could regulate inflammation and promote epithelialization, collagen deposition, and angiogenesis. In summary, this present study demonstrates that CMCS/Odex/OPC/PRP hydrogel may serve as a promising multifunctional dressing for skin wound healing.
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Quitosana , Plasma Rico em Plaquetas , Humanos , Hidrogéis/química , Quitosana/química , Preparações de Ação Retardada , Espécies Reativas de Oxigênio , Cicatrização , Antibacterianos/análise , Peptídeos e Proteínas de Sinalização Intercelular , Plasma Rico em Plaquetas/química , Concentração de Íons de HidrogênioRESUMO
Infected wounds pose a serious threat to public health and pose a significant challenge and financial burden worldwide. The treatment of infected wounds is now an urgent problem to be solved. Herein, mild hyperthermia-assisted hydrogels composed of carboxymethyl chitosan (CMCs), oxidized dextran (Odex), epigallocatechin gallate (EGCG) and PtNPs@PVP (CAT-like nanoenzymes) were proposed for the repair of infected wounds. The incorporation of PtNPs@PVP nanoenzymes give the hydrogels excellent photothermal property and CAT-like activity. When the temperature is maintained at 42-45 °C under 808 nm near infrared (NIR) exposure, the CMCs/Odex/EGCG/Nanoenzymes (COEN2) hydrogel demonstrated highly enhanced antibacterial ability (95.9 % in vivo), hydrogen peroxide (H2O2) scavenging ratio (85.1 % in vitro) and oxygen supply (20.7 mg/L in vitro). Furthermore, this mild-heat stimulation also promoted angiogenesis in the damaged skin area. Overall, this multifunctional hydrogel with antibacterial, antioxidant, oxygen supply, hemostasis, and angiogenesis capabilities has shown great promise in the repair of infected wounds. This study establishes the paradigm of enhanced infected wound healing by mild hyperthermia-assisted H2O2 scavenging, oxygen supplemental, and photothermal antibacterial hydrogels.
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Quitosana , Hipertermia Induzida , Infecção dos Ferimentos , Humanos , Hidrogéis/farmacologia , Peróxido de Hidrogênio , Infecção dos Ferimentos/tratamento farmacológico , Oxigênio , Antibacterianos/farmacologia , CicatrizaçãoRESUMO
NIK plays a crucial role in the noncanonical NF-κB signaling pathway associated with diverse inflammatory and autoimmune diseases. Our study presents compound 54, a novel NIK inhibitor, designed through a structure-based scaffold-hopping approach from the previously identified B022. Compound 54 demonstrates remarkable selectivity and potency against NIK both in vitro and in vivo, effectively suppressing pro-inflammatory cytokines and nitric oxide production. In mouse models, compound 54 protected against LPS-induced systemic sepsis, reducing AST, ALT, and AKP liver injury markers. Additionally, it also attenuates sepsis-induced lung and kidney damage. Mechanistically, compound 54 blocks the noncanonical NF-κB signaling pathway by targeting NIK, preventing p100 to p52 processing. This work reveals a novel class of NIK inhibitors with significant potential for sepsis therapy.
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Proteínas Serina-Treonina Quinases , Sepse , Animais , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , NF-kappa B/metabolismo , Quinase Induzida por NF-kappaB , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sepse/induzido quimicamente , Sepse/tratamento farmacológicoRESUMO
In this study, eight lindenane-type sesquiterpene dimers, including five previously undescribed sesquiterpene dimers (1-5), were isolated from the roots of Chloranthus fortunei, and their structures were elucidated using 1D/2D NMR, HRESIMS, and ECD calculations. Compound 1 presents the second example of a type of novel 8,9-seco lindenane-type sesquiterpene dimer, considered a product of 8/9-diketone oxidation. Compounds 2 and 3 represent the third and fourth examples, respectively, of this kind of C-11 methine dimer. Furthermore, compound 4 was considered as an artifact generated from the radical reaction of a known compound chlojaponilide F (6), which was explained by the density functional theory quantum calculation. All isolates were evaluated for their protective activity against the LPS-induced pulmonary epithelial cell line with compound 7 exhibiting the most potent bioactivity. Further in vitro biological evaluation demonstrated that 7 reduced the production of reactive oxygen species and interleukin-1ß, further regulated by the expression of the NLRP3. These results show that compound 7 exhibits therapeutic potential for lung inflammatory diseases.
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Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a life-threatening risk. Near-infrared (NIR)-assisted photothermal antibacterial combined with antioxidant hydrogel has shown significant potential in the healing of infected wounds. However, existing photothermal agents are typically metal-based, complicated to synthesize, or pose biosafety hazards. In this study, we utilized plant-derived blackcurrant extract (B) as a natural source for both photothermal and antioxidant properties. By incorporating B into a G-O hydrogel crosslinked through Schiff base reaction between gelatin (G) and oxidized pullulan (O), the resulting G-O-B hydrogel exhibited good injectability and biocompatibility along with robust photothermal and antioxidant activities. Upon NIR irradiation, the controlled temperature (around 45-50 °C) generated by the G-O-B hydrogel resulted in rapid (10 min) and efficient killing of Staphylococcus aureus (99 %), Escherichia coli (98 %), and Pseudomonas aeruginosa (82 %). Furthermore, the G-O-B0.5 hydrogel containing 0.5 % blackcurrant extract promoted collagen deposition, angiogenesis, and accelerated burn wound closure conclusively, demonstrating that this well-designed and extract-contained hydrogel dressing holds immense potential for enhancing the healing process of bacterial-infected burn wounds.