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The translation of Fe-based agents for ferroptosis tumor therapy is restricted by the unstable iron valence state, the harsh catalytic environment, and the complex tumor self-protection mechanism. Herein, we developed a stable nickel-based single-atom-metal-clusters (NSAMCs) biocatalyst for efficient tumor ferroptosis therapy. NSAMCs with a nanowire-like nanostructure and hydrophilic functional groups exhibit good water-solubility, colloidal stability, negligible systemic toxicity, and target specificity. In particular, NSAMCs possess excellent peroxidase-like and glutathione oxidase-like activities through the synergistic influence between metal clusters and single atoms. The dual-enzymatic performance enables NSAMCs to synergistically promote efficient ferroptosis of cancer cells through lipid peroxidization aggregation and glutathione peroxidase 4 inactivation. Importantly, NSAMCs highlight the boost of ferroptosis tumor therapy via the synergistic effect between single-atoms and metal clusters, providing a practical and feasible paradigm for further improving the efficiency of ferroptosis tumor treatment.
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The rational construction of efficient hypoxia-tolerant nanocatalysts capable of generating singlet oxygen (1O2) without external stimuli is of great importance for tumor therapy. Herein, uniformly dispersed and favorable biosafety profile graphitic carbon nitride quantum dots immobilized with Fe-N4 moieties modulated by axial O atom (denoted as O-Fe-N4) are developed for converting H2O2 into 1O2 via Russell reaction, without introducing external energy. Notably, O-Fe-N4 performs two interconnected catalytic properties: glutathione oxidase-mimic activity to provide substrate for subsequent 1O2 generation, avoiding the blunting anticancer efficacy by glutathione. The O-Fe-N4 catalyst demonstrates a specific activity of 79.58 U mg-1 at pH 6.2, outperforming the most reported Fe-N4 catalysts. Density functional theory calculations demonstrate that the axial O atom can effectively modulate the relative position and electron affinity between Fe and N, lowering the activation energy, strengthening the selectivity, and thus facilitating the Russell-type reaction. The gratifying enzymatic activity stemming from the well-defined Fe-N/O structure can inhibit tumor proliferation by efficiently downregulating glutathione peroxidase 4 activity and inducing lipid peroxidation. Altogether, the O-Fe-N4 catalyst not only represents an efficient platform for self-cascaded catalysis to address the limitations of 1O2-involved cancer treatment but also provides a paradigm to enhance the performance of the Fe-N4 catalyst.
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BACKGROUND: Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. METHODS: In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. RESULTS: The baPWV was linked with VFA, waist circumference, and women's SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men's SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05). CONCLUSIONS: Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.
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Dual/multimodal imaging strategies are increasingly recognized for their potential to provide comprehensive diagnostic insights in cancer imaging by harnessing complementary data. This study presents an innovative probe that capitalizes on the synergistic benefits of afterglow luminescence and magnetic resonance imaging (MRI), effectively eliminating autofluorescence interference and delivering a superior signal-to-noise ratio. Additionally, it facilitates deep tissue penetration and enables noninvasive imaging. Despite the advantages, only a limited number of probes have demonstrated the capability to simultaneously enhance afterglow luminescence and achieve high-resolution MRI and afterglow imaging. Herein, we introduce a cutting-edge imaging platform based on semiconducting polymer nanoparticles (PFODBT) integrated with NaYF4@NaGdF4 (Y@Gd@PFO-SPNs), which can directly amplify afterglow luminescence and generate MRI and afterglow signals in tumor tissues. The proposed mechanism involves lanthanide nanoparticles producing singlet oxygen (1O2) upon white light irradiation, which subsequently oxidizes PFODBT, thereby intensifying afterglow luminescence. This innovative platform paves the way for the development of high signal-to-background ratio imaging modalities, promising noninvasive diagnostics for cancer.
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Elementos de la Serie de los Lantanoides , Imagen por Resonancia Magnética , Nanopartículas , Polímeros , Semiconductores , Imagen por Resonancia Magnética/métodos , Animales , Elementos de la Serie de los Lantanoides/química , Polímeros/química , Nanopartículas/química , Ratones , Humanos , Gadolinio/química , Luminiscencia , Oxígeno Singlete/química , Itrio/química , Fluoruros/química , Ratones DesnudosRESUMEN
Background: Many studies have confirmed that lipid accumulation products (LAP) predict arterial stiffness (AS) in hypertensive patients. But there is little research on the use of LAP in identifying early atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to determine the relationship between the LAP index and brachial-ankle pulse wave velocity (baPWV) in Chinese patients with T2DM. Methods: A total of 1471 Chinese participants with T2DM, ranging in age from 18 to 80, were included in this cross-sectional study. BaPWV measurements were used to calculate the AS. A baPWV greater than the 75th percentile (1700 cm/s) was defined as indicating increased AS. The LAP index was calculated from the combination of waist circumference (WC) and triglycerides (TG). Results: According to the quartiles of the LAP index, baPWV tended to increase after adjusting for sex and age. Multiple linear regression analysis showed that the beta coefficient (ß) of baPWV increased by 31.0 cm/s for each unit of lnLAP that was increased, and the 95% confidence interval (CI) was (6.5, 55.5) cm/s. In multivariate logistic regression analyses, after fully adjusting for confounders, the risk of elevated baPWV increased with each unit increase in lnLAP, with an odds ratio (OR) of 1.3 (95% CI: 1.0, 1.8). According to the generalized additive model (GAM), we found that lnLAP was positively correlated with baPWV and baPWV elevation. The results were the same for males and females. Subgroup analyses showed that the positive correlation between lnLAP and elevated baPWV did not interact across all subgroups. Conclusions: In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.
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Diabetes Mellitus Tipo 2 , Producto de la Acumulación de Lípidos , Rigidez Vascular , Masculino , Femenino , Humanos , Índice Tobillo Braquial , Factores de Riesgo , Estudios Transversales , Análisis de la Onda del Pulso , China/epidemiologíaRESUMEN
The ratoon rice cropping system (RR) is developing rapidly in China due to its comparable annual yield and lower agricultural and labor inputs than the double rice cropping system (DR). Here, to further compare the greenhouse effects of RR and DR, a two-year field experiment was carried out in Hubei Province, central China. The ratoon season showed significantly lower cumulative CH4 emissions than the main season of RR, the early season and late season of DR. RR led to significantly lower annual cumulative CH4 emissions, but no significant difference in cumulative annual N2O emissions compared with DR. In RR, the main and ratoon seasons had significantly higher and lower grain yields than the early and late seasons of DR, respectively, resulting in comparable annual grain yields between the two systems. In addition, the ratoon season had significantly lower global warming potential (GWP) and greenhouse gas intensity-based grain yield (GHGI) than the main and late seasons. The annual GWP and GHGI of RR were significantly lower than those of DR. In general, the differences in annual CH4 emissions, GWP, and GHGI could be primarily attributed to the differences between the ratoon season and the late season. Moreover, GWP and GHGI exhibited significant positive correlations with cumulative emissions of CH4 rather than N2O. The leaf area index (LAI) and biomass accumulation in the ratoon season were significantly lower than those in the main season and late season, and CH4 emissions, GWP, and GHGI showed significant positive correlations with LAI, biomass accumulation and grain yield in the ratoon and late season. Finally, RR had significantly higher net ecosystem economic benefits (NEEB) than DR. Overall, this study indicates that RR is a green cropping system with lower annual CH4 emissions, GWP, and GHGI as well as higher NEEB.
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Processing transition metal carbides/nitrides (MXenes) inks into large-area functional coatings expects promising potential for electromagnetic interference (EMI) shielding and infrared stealth. However, the coating performances, especially for scalable fabrication techniques, are greatly constrained by the flake size and stacking manner of MXene. Herein, the large-area production of highly densified and oriented MXene coatings is demonstrated by engineering interfacial interactions of small MXene flakes with catecholamine molecules. The catecholamine molecules can micro-crosslink MXene nanosheets, significantly improving the ink's rheological properties. It favors the shear-induced sheet arrangement and inhibition of structural defects in the blade coating process, making it possible to achieve high orientation and densification of MXene assembly by either large-area coating or patterned printing. Interestingly, the MXene/catecholamine coating exhibits high conductivity of up to 12â¯247 S cm-1 and ultrahigh specific EMI shielding effectiveness of 2.0 ×10 5 dB cm2 g-1 , obviously superior to most of the reported MXene materials. Furthermore, the regularly assembled structure also endows the MXene coatings with low infrared emissivities for infrared stealth applications. Therefore, MXene/catecholamine coatings with ultraefficient EMI shielding and low infrared emissivity prove the feasibility of applications in aerospace, military, and wearable devices.
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Nanoparticles are widely used in the biomedical field for diagnostic and therapeutic purposes due to their small size, high carrier capacity, and ease of modification, which enable selective targeting and as contrast agents. Over the past decades, more and more nanoparticles have received regulatory approval to enter the clinic, more nanoparticles have shown potential for clinical translation, and humans have increasing access to them. However, nanoparticles have a high potential to cause unpredictable adverse effects on human organs, tissues, and cells due to their unique physicochemical properties and interactions with DNA, lipids, cells, tissues, proteins, and biological fluids. Currently, issues, such as nanoparticle side effects and toxicity, remain controversial, and these pitfalls must be fully considered prior to their application to body systems. Therefore, it is particularly urgent and important to assess the safety of nanoparticles acting in living organisms. In this paper, we review the important factors influencing the biosafety of nanoparticles in terms of their properties, and introduce common methods to summarize the biosafety evaluation of nanoparticles through in vitro and in body systems (AU)
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Humanos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Neoplasias/tratamiento farmacológico , SeguridadRESUMEN
Purpose: To explore the correlation between Chinese visceral adipose index (CVAI) and urinary microalbumin/creatinine ratio (UACR) and urinary albumin, and whether there is any difference in correlation between Han and Tujia ethnicity. Methods: This cross-sectional study was conducted in Changde, Hunan, China from May 2021 to December 2021. Biochemical indicators including anthropometric parameters, blood pressure, blood glucose, blood lipids, and UACR of the participants were measured. Univariate analysis, multivariate analyses and multinomial logistic regression analysis were carried out to assess the association between CVAI and albuminuria. In addition, curve fitting and threshold effect analysis were used to explore the nonlinear association between CVAI and albuminuria, and to observe whether there were ethnic differences in this association. Results: A total of 2026 adult residents were enrolled in this study, 500 of whom had albuminuria. Population-standardized prevalence of albuminuria is 19.06%. In the multivariable model adjusted for confounding factors, the odds ratio (OR) of albuminuria for pre-unit increase of CVAI and pre-SD increase of CVAI were 1.007 (1.003-1.010) and 1.298 (1.127-1.496), respectively. Multinomial logistic regression analysis confirmed the robustness and consistency of the results.The generalized additive model showed that CVAI and albuminuria had a nonlinear relationship with inflection point at 97.201 using the threshold effect. Compared with Han ethnic groups, the threshold between CVAI and albuminuria in Tujia people moved backward. The thresholds were 159.785 and 98.527, respectively. Conclusion: There was a positive nonlinear dose-response relationship between increased CVAI and higher levels of albuminuria. Maintaining appropriate CVAI levels may be important for the prevention of albuminuria.
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Nanoparticles are widely used in the biomedical field for diagnostic and therapeutic purposes due to their small size, high carrier capacity, and ease of modification, which enable selective targeting and as contrast agents. Over the past decades, more and more nanoparticles have received regulatory approval to enter the clinic, more nanoparticles have shown potential for clinical translation, and humans have increasing access to them. However, nanoparticles have a high potential to cause unpredictable adverse effects on human organs, tissues, and cells due to their unique physicochemical properties and interactions with DNA, lipids, cells, tissues, proteins, and biological fluids. Currently, issues, such as nanoparticle side effects and toxicity, remain controversial, and these pitfalls must be fully considered prior to their application to body systems. Therefore, it is particularly urgent and important to assess the safety of nanoparticles acting in living organisms. In this paper, we review the important factors influencing the biosafety of nanoparticles in terms of their properties, and introduce common methods to summarize the biosafety evaluation of nanoparticles through in vitro and in body systems.
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Nanopartículas , Neoplasias , Humanos , Contención de Riesgos Biológicos , Nanopartículas/uso terapéutico , Sistemas de Liberación de Medicamentos/efectos adversos , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/diagnósticoRESUMEN
INTRODUCTION: Abdominal infection combined with pneumoperitoneum after renal transplantation is rare, clinically confusing, and easily misdiagnosed by physicians as gastrointestinal perforation. PATIENT CONCERNS: A 54-year-old man experienced abdominal pain and distension together with signs of peritoneal irritation after cadaveric renal transplantation. CT and standing abdominal plain film showed a large pneumoperitoneum in the abdominal cavity and the patient underwent an exploratory laparotomy but no gastrointestinal perforation was found. DIAGNOSIS: No gastrointestinal perforation was found during the operation. In the search for the infectious agent, ascites culture was negative while next-generation sequencing was positive, suggesting the presence of intestinal flora ectopic to abdominal infection with anaerobic respiration fermentation leading to large amounts of gas. INTERVENTIONS: The patient underwent exploratory laparotomy without gastrointestinal perforation, and then underwent abdominal lavage, placed abdominal drainage tube, and conducted culture and next-generation sequencing examination of ascites. OUTCOMES: Postoperative symptoms were relieved and intestinal function recovered. After 3 months of outpatient follow-up, the patient had stable transplanted kidney function and was in good spirits and sleeping well, with a good appetite, soft and regular stools, no abdominal pain and distension, and no fever. CONCLUSION: Patients after kidney transplantation should be wary of abdominal infection being misdiagnosed as gastrointestinal perforation.
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Traumatismos Abdominales , Perforación Intestinal , Infecciones Intraabdominales , Trasplante de Riñón , Neumoperitoneo , Masculino , Humanos , Persona de Mediana Edad , Trasplante de Riñón/efectos adversos , Neumoperitoneo/etiología , Ascitis/complicaciones , Infecciones Intraabdominales/complicaciones , Traumatismos Abdominales/complicaciones , Peritoneo , Dolor Abdominal , Perforación Intestinal/etiologíaRESUMEN
Purpose: The best predictors and cut points for metabolic syndrome (MetS) in Chinese patients with type 2 diabetes (T2DM) were determined by comparing six anthropometric measures: body mass index (BMI), triglyceride-glucose (TyG), the product of TyG and waist-to-hip ratio (TyG-WHpR), the product of TyG and waist-to-height ratio (TyG-WHtR), the product of TyG and waist circumference (TyG-WC), and the product of TyG and body mass index (TyG-BMI). Patients and Methods: Sixteen hundred and sixty-five adult patients with T2DM were collected, and the ability and cut points of each index to predict MetS were compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) values. Then, logistic regression analysis was used to adjust for confounders, including adjustment for menopause in women, to obtain the odds ratio (OR) and 95% confidence interval (CI). Results: MetS was present in 71.60% of T2DM patients, 75.00% of men, and 67.02% of women. BMI was the best predictor of MetS in men with T2DM (AUC = 0.8646, 95% CI: 0.8379-0.8912), with a cut point of 24.5500 kg/m2 (specificity: 0.7714; sensitivity: 0.7533), and TyG-WC was the best predictor of MetS in women with T2DM (AUC = 0.8362, 95% CI: 0.8034-0.8690), with a cut point of 154.1548 (specificity: 0.7455; sensitivity: 0.8076). Conclusion: The best predictor of MetS in adults with T2DM is BMI with a cut point of 24.5500 kg/m2 for men and TyG-WC with a cut point of 154.1548 for women.
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An ultrasensitive electrochemical immunosensor based on signal amplification of the deposition of the electroactive ferrocene-tyramine (Fc-Tyr) molecule, catalyzed by horseradish peroxidase (HRP), was constructed for the detection of the liver cancer marker Glypican-3 (GPC3). Functional electroactive molecule Fc-Tyr is reported to exhibit both the enzymatic cascade catalytic activity of tyramine signal amplification (TSA) and the excellent redox properties of ferrocene. In terms of design, the low matrix effects inherent in using the magnetic bead platforms, a quasi-homogeneous system, allowed capturing the target protein GPC3 without sample pretreatment, and loading HRP to trigger the TSA, which induced a large amount of Fc-Tyr deposited on the electrode surface layer by layer as a signal probe for the detection of GPC3. The concept of Fc-Tyr as an electroactive label was validated, GPC3 biosensor exhibited high selectivity and sensitivity to GPC3 in the range of 0.1 ng mL-1-1 µg mL-1. Finally, the sensor was used simultaneously with ELISA to assess GPC3 levels in the serum of clinical liver cancer patients, and the results showed consistency, with a recovery of 98.33-105.35% and a relative standard deviation (RSD) of 4.38-8.18%, providing a theoretical basis for achieving portable, rapid and point of care testing (POCT) of tumor markers.
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Técnicas Biosensibles , Neoplasias Hepáticas , Nanopartículas del Metal , Humanos , Inmunoensayo/métodos , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , Metalocenos , Glipicanos , Peroxidasa de Rábano Silvestre/química , Neoplasias Hepáticas/diagnóstico , Tiramina/química , Técnicas Electroquímicas , Oro/química , Límite de DetecciónRESUMEN
Solution processing of two-dimensional nanomaterial inks guarantees efficient, straightforward fabrication of functional films, coatings, flexible devices, etc. Despite the excellent solution processibility and viscoelasticity of MXene aqueous inks, formulation of nonaqueous MXene inks with great affinity to both hydrophilic and hydrophobic substrates has proven quite challenging, limiting the practical applications of MXenes in printing/coatings on various substrates. Here, MXene surface chemistry is manipulated by asymmetrically grafting polystyrene and further concentrating the flakes into additive-free Janus MXene organic inks. The modified MXene nanosheets exhibit hydrophilicity on one side and hydrophobicity on the other. As a result, Janus MXene nanosheets ensure broad dispersibility in polar and nonpolar solvents, which in turn greatly extends the ink shelf life by slowing down the oxidation kinetics. Janus MXene sheets dispersed in toluene at room temperature remain at 90% of the initial solids after 1 month of storage. Janus surface engineering on MXene flakes guarantees the straightforward formation of uniform yet firm, large-area coatings on hydrophilic or hydrophobic substrates. These coatings demonstrate improved photothermal properties and chemical stability as well as good electromagnetic interference shielding performance. This strategy provides a simple and cost-effective way to promote the performance of MXene electronics in a variety of applications.
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The direct 3D printing of ultralight architectures with ultralow-concentration 2D nanomaterial inks is necessary yet challenging. Here, we describe an emulsion-based ink for direct printing using 2D nanomaterials, i.e., MXene and graphene oxide (GO). The electrostatic interactions between the ligands in the oil phase and the 2D nanomaterials in the aqueous phase help form sheet-like surfactants at the interface. The interactions between the anchored ligands among different droplets dictate the rheological characteristics of inks, enabling a gel-like behavior ideally suitable for 3D printing at ultralow concentrations of 2D nanomaterials. The 3D printed foams possess lightweight structures with densities of 2.8 mg cm-3 (GO-based) and 4.1 mg cm-3 (MXene-based), and the latter integrates outstanding electrical conductivity, electromagnetic shielding performance, and thermal insulation comparable to air. This work describes a general approach for direct-printing ultralight porous structures that take advantage of the inherent properties of 2D building blocks.
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Lanthanide based upconversion (UC) nanoprobes have emerged as promising agents for biological applications. Extending the excitation light to the second near-infrared (NIR-II), instead of the traditional 980/808 nm light, and realizing NIR-II responsive single-band red UC emission is highly demanded for bioimaging application, which has not yet been explored. Here, a new type of NIR-II (1532 nm) light responsive UC nanoparticles (UCNPs) with enhanced single-band red UC emission and controllable phase and size is designed by introducing Er3+ as sensitizer and utilizing Mn2+ as energy manipulator. Through tuning the content of Mn2+ in NaLnF4 :Er/Mn, the crystal phase, size, and emitting color are readily controlled, and the red-to-green (R/G) ratio is significantly increased from ≈20 to ≈300, leading to NIR-II responsive single band red emission via efficient energy transfer between Er3+ and Mn2+ . In addition, the single band red emitting intensity can be further improved by coating shell to avoid the surface quenching effect. More importantly, NIR-II light activated red UC bioimaging and photodynamic therapy through loading photosensitizer of zinc phthalocyanine are successfully achieved for the first time. These findings provide a new strategy of designing NIR-II light responsive single-band red emissive UCNPs for biomedical applications.
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Elementos de la Serie de los Lantanoides , Nanopartículas , Fotoquimioterapia , Luminiscencia , Luz , Nanopartículas/químicaRESUMEN
Two-dimensional transition metal carbide/nitride (MXene) conductive inks are promising for scalable production of printable electronics, electromagnetic devices, and multifunctional coatings. However, the susceptible oxidation and poor rheological property seriously impede the printability of MXene inks and the exploration of functional devices. Here, we proposed a controllable surface grafting strategy for MXene flakes (p-MXene) with prepolymerized polydopamine macromolecules to protect against water and oxygen, enrich surface chemistry, and significantly optimize the rheological properties of the inks. The obtained p-MXene inks can adapt to screen-printing and other high-viscosity processing techniques, facilitating the development of patterned electromagnetic films and coatings. Interestingly, the printed MXene polarizer can freely switch and quantitatively control microwave transmission, giving an inspiring means for smart microwave modulation beyond the commonly reported shielding function. Moreover, the introduction of polydopamine nanoshell enables the infrared emissivity of MXene coating to be adjusted to a large extent, which can produce infrared anti-counterfeiting patterns in a thermal imager. Therefore, multifunctional antioxidant p-MXene inks will greatly extend the potential applications for the next-generation printable electronics and devices.
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Excessive production of hydrogen sulfide (H2 S) plays a crucial role in the progress of colon cancer. Construction of tumor-specific H2 S-activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2 S triggered Co-doped polyoxometalate (POM-Co) cluster with self-adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2 S/glutathione (GSH) is designed for synergistic enhanced tumor-specific photothermal and chemodynamic therapy. The designed POM-Co nanocluster holds H2 S responsive "turn-on" photothermal property in colon cancer via self-assembling to form large-sized POM-CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM-CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)-catalyzed â¢OH production and Russell mechanism-enabled 1 O2 generation with GSH consumption, respectively. More importantly, the degraded POM-CoS is reactivated by endogenous H2 S for recyclable and sustainable consumption of H2 S and GSH, resulting in tumor-specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment-driven nanoprobes with controllable biodegradation for precise and sustainable anti-tumor therapy.
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Neoplasias del Colon , Nanopartículas , Técnicas Fotoacústicas , Humanos , Fototerapia/métodos , Neoplasias del Colon/terapia , Glutatión/metabolismo , Microambiente TumoralRESUMEN
In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20-fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment-enabled in situ silver-based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB-enabled intratumoral nanosynthetic medicine, intratumoral H2 O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB-unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2 O2 . Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably-elevated anti-tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.