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Chemotherapy-based combination regimens are recommended as first-line treatment for colorectal cancer. However, multidrug resistance (MDR) and limited drug infiltration in tumor microenvironment remain critical challenges. Herein, a pH/redox dual activated supramolecular DAS@CD-OxPt (IV) nanoparticles (NPs) via host-guest molecular recognition to achieve relay drugs delivery of active oxaliplatin (OxPt (IV)) and Src inhibitor dasatinib (DAS) between tumor cells is developed. DAS@CD-OxPt (IV) NPs exhibit prolonged circulation in the blood and intra-tumoral retention. Triggered by the endo/lysosome (pH 5.0), flexible DAS@CD-OxPt (IV) NPs exhibited proton-driven in situ assembly to form nanofiber in tumor cells. Dual chemotherapeutic agents released from DAS@CD-OxPt (IV) NPs synergistically cause irreversible DNA damage by blocking p53-mediated DNA repair. Supramolecular nanofibers can further serve as the "ammunition depot" to continuously release drugs from dying cells and transport them into neighboring tumor cells, leading to domino-like cell death and enhanced immunogenicity. Furthermore, DAS@CD-OxPt (IV) NPs combined with immune checkpoint blockade (ICB) therapy strikingly suppress CT26 tumor growth and pulmonary metastasis.
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The formation mechanism behind the sophisticated aromas of sesame oil (SO) has not been elucidated. The interaction effects of the Maillard reaction (MR) and lipid oxidation on the aroma formation of fragrant sesame oil were investigated in model reaction systems made of l-lysine (Lys) and d-glucose (Glc) with or without fresh SO (FSO) or oxidized SO (OSO). The addition of OSO to the Lys-Glc model increased the MR browning at 294 nm and 420 nm and enhanced the DPPH radical scavenging activity greater than the addition of FSO (p < 0.05). The presence of lysine and glucose inhibited the oxidation of sesame oil, reduced the loss of γ-tocopherol, and facilitated the formation of sesamol (p < 0.05). The Maillard-lipid interaction led to the increased concentrations of some of the alkylpyrazines, alkylfurans, and MR-derived ketones and acids (p < 0.05) while reducing the concentrations of other pyrazines, lipid-derived furans, aliphatic aldehydes, ketones, alcohols, and acids (p < 0.05). The addition of FSO to the MR model enhanced the characteristic roasted, nutty, sweet, and fatty aromas in sesame oil (p < 0.05), while excessive lipid oxidation (OSO) brought about an unpleasant oxidized odor and reduced the characteristic aromas. This study helps to understand the sophisticated aroma formation mechanism in sesame oil and provides scientific instruction for precise flavor control in the production of sesame oil.
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Glucosa , Lisina , Reacción de Maillard , Odorantes , Oxidación-Reducción , Aceite de Sésamo , Aceite de Sésamo/química , Glucosa/química , Odorantes/análisis , Lisina/química , Fenoles/química , BenzodioxolesRESUMEN
Accumulating evidence highlighted the important roles of platelets in the prognosis and progression of various tumors. Nevertheless, the role of platelet-related genes (PRGs) in HCC remains limited. In this work, 92 differentially expressed PRGs were described in HCC using TCGA and ICGC databases. Then, based on the different expressions of PRGs, we explored two subtypes and developed the PRGs prognostic signature in HCC. The PRGs signature was an independent prognosis factor associated with immune cell infiltration in HCC. Furthermore, two external validation sets verified the expression and prognosis of the PRGs signature gene in HCC. Finally, scRNA-seq analysis demonstrated that the signature genes (CENPE and KIF2C) were mainly expressed in cycling T cells and prolif-TAMs. Enrichment analysis showed that CENPE and KIF2C regulated the cell cycle and p53 pathways in these cells. In conclusion, this study builds the PRGs-related risk signature of HCC and reveals the potential mechanism by which these signature genes regulate the immune microenvironment in HCC.
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Amorphous oxide semiconductor thin-film transistors (AOS TFTs) are ever-increasingly utilized in displays. However, to bring high mobility and excellent stability together is a daunting challenge. Here, the carrier transport/relaxation bilayer stacked AOS TFTs are investigated to solve the mobility-stability conflict. The charge transport layer (CTL) is made of amorphous In-rich InSnZnO, which favors big average effective coordination number for all cations and more edge-shared structures for better charge transport. Praseodymium-doped InSnZnO is used as the charge relaxation layer (CRL), which substantially shortens the photoelectron lifetime as revealed by femtosecond transient absorption spectroscopy. The CTL and CRL with the thickness suitable for industrial production respectively afford minute potential barrier fluctuation for charge transport and fast relaxation for photo-generated carriers, resulting in transistors with an ultrahigh mobility (75.5 cm2 V-1 s-1 ) and small negative-bias-illumination-stress/positive-bias-temperature-stress voltage shifts (-1.64/0.76 V). The design concept provides a promising route to address the mobility-stability conflict for high-end displays.
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Crystalline Ga2O3 (c-Ga2O3) is a promising candidate for next-generation solar-blind photodetectors (SBPDs) but is suffering from high processing temperatures. Herein, seed-induced engineering is proposed via adopting Zn as an induced metal for crystallizing Ga2O3, lowering the processing temperature by 200 °C. After annealing, the Zn/Ga2O3 consists of an inner Ga2O3 layer of a monoclinic crystalline phase, top ZnO crystals coming from Zn oxidation, and a thin corundum Ga2O3 layer between them, which implies a "seed-induced" crystallization mechanism besides the nonequilibrium chaotic state caused by the traditional electron transfer one. As a result, the tailored c-Ga2O3 thin-film transistor-type SBPD with enhanced packing density and finite oxygen deficiency demonstrates a satisfactory responsivity of 8.6 A/W and also an ultrahigh UVC/visible rejection ratio (R254/R450) of 2 × 105. The seed-induced engineering forecasts its potential application in crystalline Ga2O3 SBPDs under a relatively low processing temperature.
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Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process. In this study, a hydrogen sulfide-responsive (H2S) small molecule prodrug was synthesized by linking two chemotherapy drugs, camptothecin (CPT) and gemcitabine (GT), using a reductive disulfide bond simultaneously with a lock GT strategy using a H2S-responsive azide group (denoted as N3-GT-CPT). The ingenious design endows the easy coprecipitation peculiarity of the prodrug with clinical indocyanine green (ICG) via a combined interaction force of hydrophobic, π-π stacking, and electrostatic interactions of anions and cations, thus producing a more stable and multifunctional therapeutic nanosystem. Considering the great photothermal and imaging ability of ICG, the obtained nanosystem showed an excellent therapeutic ability against colon tumors in vitro and in vivo with selective response to intercellular H2S, thus offering a good combination-based multiple therapy for treatment of tumors.
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Antineoplásicos , Nanopartículas , Profármacos , Antineoplásicos/química , Azidas , Camptotecina/química , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Verde de Indocianina/química , Nanopartículas/química , Profármacos/químicaRESUMEN
PURPOSE: Measuring heart rate recovery (HRR) holds valuable cardiovascular information and requires minimal technical skill and cost. Understanding the associations between HRR and more robust cardiovascular indicators, such as central systolic blood pressure (CSBP), can provide valuable cardiovascular information with less involvement. CSBP is a strong predictor of certain cardiovascular diseases. The study aims to examine the association between measures of HRR and CSBP and the augmentation index (AIx) in a group of young, healthy individuals and based on sex. PARTICIPANTS AND METHODS: One-hundred and seven participants (men - 55, women - 52) were measured for HRR at one minute (HRR1) and two minutes (HRR2) after maximum oxygen consumption (VO2max) testing, CSBP, and the AIx at a heart rate of 75 beatsâmin-1 (AIx@75). RESULTS: The Pearson correlation indicated no association between HRR1, HRR2, and CSBP in men and women combined: r = 0.06, P = 0.53; r = 0.05, P = 0.59, respectively, or based on sex: men = r = 0.01, P = 0.95; r = 0.04, P = 0.79, respectively, and women = r = -0.05, P = 0.75; r = -0.09, P = 0.52, respectively. However, there were associations between HRR1 and AIx@75 in men and women combined: r = -0.37, P < 0.001, and based on sex: men = r = -0.31, P = 0.02, and women = r = -0.38, P < 0.01. CONCLUSION: Measures of HRR were not associated with CSBP in a combined group of young men and women or based on sex. Most measures of HRR, especially those established by parasympathetic nervous activity, were associated with lower AIx@75. Though measures of HRR might be good indicators of cardiovascular disease, they might not be good indicators of CSBP in young, healthy individuals.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , MasculinoRESUMEN
Oxygen diffusivity and surface exchange kinetics underpin the ionic, electronic, and catalytic functionalities of complex multivalent oxides. Towards understanding and controlling the kinetics of oxygen transport in emerging technologies, it is highly desirable to reveal the underlying lattice dynamics and ionic activities related to oxygen variation. In this study, the evolution of oxygen content is identified in real-time during the progress of a topotactic phase transition in La0.7 Sr0.3 MnO3-δ epitaxial thin films, both at the surface and throughout the bulk. Using polarized neutron reflectometry, a quantitative depth profile of the oxygen content gradient is achieved, which, alongside atomic-resolution scanning transmission electron microscopy, uniquely reveals the formation of a novel structural phase near the surface. Surface-sensitive X-ray spectroscopies further confirm a significant change of the electronic structure accompanying the transition. The anisotropic features of this novel phase enable a distinct oxygen diffusion pathway in contrast to conventional observation of oxygen motion at moderate temperatures. The results provide insights furthering the design of solid oxygen ion conductors within the framework of topotactic phase transitions.
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Optoelectronic synaptic devices are of great scientific and practical importance because of various potential applications such as ocular simulating and optical-electrical managers based on a new optoelectronic coupling mechanism. In this work, we design a novel channel layer with p-type CsPbBr3 nanoparticles (NPs) buried in an InGaZnO (IGZO) film to construct the corresponding thin-film transistors (TFTs), which exhibits intense improvement in visible-light photosensitivity and synaptic plasticity as compared to the pure IGZO counterpart. Specifically, the composite device is able to exhibit versatile synaptic behavior under light stimuli with density as low as 0.12 µW/cm2 and with the gain 5-20 times higher than that of the IGZO TFT in the visible-light region. Based on the band alignment between the IGZO and NPs, the excitation and decay processes of intrinsic and photoinduced carriers are discussed. Moreover, owing to the gate bias control in a three-terminal configuration, our TFT synapses can imitate complex biological behaviors including the famous "Pavlov's dog" experiment and the "reward and punishment mechanism" of the brain via editing the gate voltage/light pulse stimuli.
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OBJECTIVE: Necrotising soft-tissue infection is a rare but life-threatening infectious disease with high morbidity and mortality. It is typically caused by toxin-producing bacteria and characterised clinically by a very rapid progression of the disease with significant local tissue destruction. In this study, we intend to explore effective wound management to control the invasive infection and to decrease the high mortality. METHOD: This retrospective analysis explored the wound management and mortality in patients with necrotising soft-tissue infection. Extensive debridement, vacuum sealing drainage (VSD) with normal saline instillation combined with broad-spectrum or sensitive antibiotics, and supportive therapies were used. RESULTS: All 17 patients included in the analysis survived. The microbiology of 11 patients was found to be polymicrobial. Of the patients, 14 were discharged with completely healed wounds and three were transferred to a local hospital after the systemic and invasive wound infection was controlled. CONCLUSION: Our experiences revealed the outstanding effect of VSD with instillation in removing the debris of necrotising tissue on the wound bed, in the continual and complete drainage of wound exudates, and in prompting wound healing.
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Desbridamiento , Drenaje , Terapia de Presión Negativa para Heridas/métodos , Infecciones de los Tejidos Blandos/terapia , Vacio , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante de Piel , Infecciones de los Tejidos Blandos/microbiología , Resultado del TratamientoRESUMEN
BACKGROUND: Electronic devices which mimic the functionality of biological synapses are a large step to replicate the human brain for neuromorphic computing and for numerous medical research investigations. One of the representative synaptic behaviors is paired-pulse facilitation (PPF). It has been widely investigated because it is regarded to be related to biological memory. However, plasticity behavior is only part of the human brain memory behavior. METHODS: Here, we present a phenomenon which is opposite to PPF, i.e., paired-pulse inhibition (PPI), in nano oxide devices for the first time. The research here suggests that rather than being enhanced, the phenomena of memory loss would also be possessed by such electronic devices. The device physics mechanism behind memory loss behavior was investigated. This mechanism is sustained by historical memory and degradation manufactured by device trauma to regulate characteristically stimulated origins of artificial transmission behaviors. RESULTS: Under the trauma of a memory device, both the signal amplitude and signal time stimulated by a pulse are lower than the first signal stimulated by a previous pulse in the PPF, representing a new scenario in the struggle for memory. In this way, more typical human brain behaviors could be simulated, including the effect of age on latency and error generation, cerebellar infarct, trauma and memory loss pharmacological actions (such as those caused by hyoscines and nitrazepam). CONCLUSION: Thus, this study developed a new approach for implementing the manner in which the brain works in semiconductor devices for improving medical research.
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Semiconductores , Sinapsis/fisiología , Biomimética , Encéfalo/fisiología , Diseño de Equipo , Nanoestructuras , Plasticidad Neuronal , Óxidos/metabolismoRESUMEN
BACKGROUND: A novel temperature dependent amorphous nano oxide semiconductor (AOS) thin-film transistor (TFT) is reported here for the first time, which is vastly different from conventional behavior. In the literature, the threshold voltage of TFTs decreases with increasing temperature. Here, the threshold voltage increased at higher temperatures, which is different from previously reported results and was repeated on different samples. METHODS: Electrical experiments (such as I-V measurements and photoelectron spectrometer experiments) were performed in order to explain such behavior. Double sweeping gate voltage measurements were performed to investigate the mechanism for the temperature dependent behavior. RESULTS: It was found that there was a change of trap charge under thermal stress, which was released after the stress. CONCLUSION: Non-Arrhenius behaviors (including a linear behavior) were obtained for the amorphous nano oxide thin-film transistors within 303~425 K, suggesting their potential to be adjusted by measurement processes and be applied as temperature sensors for numerous medical applications.
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Nanoestructuras/química , Semiconductores , Electricidad , Calor , Óxidos , Espectroscopía de FotoelectronesRESUMEN
In this work, a Co-N doped carbon nanotube (CNT) catalyst was fabricated via a simple pyrolysis approach and the effects of solvothermal processing on the catalytic activity of the as-prepared material were investigated in detail. The results show that after solvothermal processing (Co-NC) the catalyst has a more homogeneous anemone structure, a higher nitrogen content, a larger BET surface area and a higher degree of graphitization compared to the catalyst produced after non-solvothermal processing (Co-MA). The results of electrochemical tests indicate that Co-NC, compared to commercial 20% Pt/C and Co-MA, has an improved mass transfer process and sufficient active site exposure, which brings about superb oxygen reduction electrocatalytic activity, a higher reduction potential (-0.2 V vs. Ag/AgCl), a limiting diffusion current (5.44 mA cm-2) and excellent stability in 0.1 M KOH solution.
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Angiopoietin-like protein 3 (Angptl3)lipoprotein lipase (LPL) pathway may be a useful pharmacologic target for hyperlipidemia. The present study was conducted to test the effect of soluble fiber extracted from Undaria pinnatifida (UP), on hyperlipidemia in apolipoprotein E-deficient (ApoE−/−) mice. Forty mice were divided into four groups (n = 10): control group (C57BL/6J mice), ApoE−/− mice group, and two groups of ApoE−/− mice treated with UP fiber (5 or 10 % per day). UP soluble fiber treatment significantly decreased plasma and hepatic total cholesterol, triglycerides levels, plasma low-density lipoprotein cholesterol, and malondialdehyde concentrations and increased plasma high-density lipoprotein cholesterol level and downregulated protein expression of Angptl3 concomitantly with upregulated protein expression of LPL. In addition, T0901317 caused elevated expression of hepatic Angptl3 protein, and the effect of T0901317 was also abrogated by UP soluble fiber in C57BL/6J mice. The present results suggest that the UP soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice (AU)
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Animales , Ratas , Undaria , Angiopoyetinas/farmacocinética , Hiperlipidemias/tratamiento farmacológico , Apolipoproteínas E/deficiencia , Algas Marinas , Estudios de Casos y Controles , Sustancias Protectoras/farmacocinética , Modelos Animales de EnfermedadRESUMEN
Angiopoietin-like protein 3 (Angptl3)-lipoprotein lipase (LPL) pathway may be a useful pharmacologic target for hyperlipidemia. The present study was conducted to test the effect of soluble fiber extracted from Undaria pinnatifida (UP), on hyperlipidemia in apolipoprotein E-deficient (ApoE(-/-)) mice. Forty mice were divided into four groups (n = 10): control group (C57BL/6J mice), ApoE(-/-) mice group, and two groups of ApoE(-/-) mice treated with UP fiber (5 or 10 % per day). UP soluble fiber treatment significantly decreased plasma and hepatic total cholesterol, triglycerides levels, plasma low-density lipoprotein cholesterol, and malondialdehyde concentrations and increased plasma high-density lipoprotein cholesterol level and downregulated protein expression of Angptl3 concomitantly with upregulated protein expression of LPL. In addition, T0901317 caused elevated expression of hepatic Angptl3 protein, and the effect of T0901317 was also abrogated by UP soluble fiber in C57BL/6J mice. The present results suggest that the UP soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.
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Angiopoyetinas/metabolismo , Fibras de la Dieta/administración & dosificación , Hiperlipidemias/dietoterapia , Hiperlipidemias/metabolismo , Lipoproteína Lipasa/metabolismo , Hígado/efectos de los fármacos , Undaria/química , Proteína 3 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Angiopoyetinas/antagonistas & inhibidores , Angiopoyetinas/genética , Animales , Anticolesterolemiantes/farmacología , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Regulación de la Expresión Génica , Hidrocarburos Fluorados/farmacología , Hiperlipidemias/genética , Hiperlipidemias/patología , Lipoproteína Lipasa/genética , Hígado/metabolismo , Hígado/patología , Malondialdehído/sangre , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal/efectos de los fármacos , Solubilidad , Sulfonamidas/farmacología , Triglicéridos/sangreRESUMEN
BACKGROUND: Inhibiting the action of proprotein convertase subtilisin/kexin type 9 (PCSK9) on the low-density lipoprotein receptor (LDLR) has emerged as a novel therapeutic target for hypercholesterolemia. Here we investigated the effect of berberine, natural plant extracts, on PCSK9-LDLR pathway in C57BL/6 mice with lipopolysaccharide (LPS) induced inflammation. METHODS: Forty female mice were divided into four groups (n =10): control, LPS (5 mg/kg), LPS + berberine 10 (5 mg/kg LPS plus 10 mg/kg berberine), and LPS + berberine 30 (5 mg/kg LPS plus 30 mg/kg berberine). Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; pro-inflammatory cytokines [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)], 8-isoprostane, hepatic expressions of PCSK9 and LDLR were determined. RESULTS: Berberine pretreatment reduced the expression of hepatic PCSK9, decreased the plasma TC, TG, LDL-C, IFNγ, TNFα, IL-1α, and 8-isoprostane concentrations; increased HDL-C level and LDLR expression in mice. CONCLUSION: The present results suggest that berberine inhibits dyslipidemia in C57BL/6 mice with LPS induced inflammation through regulating PCSK9-LDLR pathway.
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Berberina/farmacología , Dislipidemias/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Dinoprost/análogos & derivados , Dinoprost/sangre , Dinoprost/metabolismo , Dislipidemias/inducido químicamente , Dislipidemias/metabolismo , Femenino , Inflamación/inducido químicamente , Inflamación/metabolismo , Interferón gamma/metabolismo , Interleucina-1alfa/metabolismo , Lípidos/sangre , Lipopolisacáridos , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/farmacología , Proproteína Convertasa 9 , Proproteína Convertasas/metabolismo , Receptores de LDL/metabolismo , Serina Endopeptidasas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE(-/-)) mice treated or not with kaempferol (50 or 100mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE(-/-) mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE(-/-) mice.