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The ideal electrolyte for the widely used LiNi0.8Mn0.1Co0.1O2 (NMC811)||graphite lithium-ion batteries is expected to have the capability of supporting higher voltages (≥4.5 volts), fast charging (≤15 minutes), charging/discharging over a wide temperature range (±60 degrees Celsius) without lithium plating, and non-flammability1-4. No existing electrolyte simultaneously meets all these requirements and electrolyte design is hindered by the absence of an effective guiding principle that addresses the relationships between battery performance, solvation structure and solid-electrolyte-interphase chemistry5. Here we report and validate an electrolyte design strategy based on a group of soft solvents that strikes a balance between weak Li+-solvent interactions, sufficient salt dissociation and desired electrochemistry to fulfil all the aforementioned requirements. Remarkably, the 4.5-volt NMC811||graphite coin cells with areal capacities of more than 2.5 milliampere hours per square centimetre retain 75 per cent (54 per cent) of their room-temperature capacity when these cells are charged and discharged at -50 degrees Celsius (-60 degrees Celsius) at a C rate of 0.1C, and the NMC811||graphite pouch cells with lean electrolyte (2.5 grams per ampere hour) achieve stable cycling with an average Coulombic efficiency of more than 99.9 per cent at -30 degrees Celsius. The comprehensive analysis further reveals an impedance matching between the NMC811 cathode and the graphite anode owing to the formation of similar lithium-fluoride-rich interphases, thus effectively avoiding lithium plating at low temperatures. This electrolyte design principle can be extended to other alkali-metal-ion batteries operating under extreme conditions.
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Copper-based nanozymes exhibit excellent antitumor activity but are easily inactivated due to the disturbance of proteins or other macromolecules with sulfhydryl. A tumor microenvironment-responsive CuMnO@Fe3O4 (CMF) core-shell nanozyme for highly efficient tumor theranostics is developed. A platelet-derived growth factor receptor-ß-recognizing cyclic peptide (PDGFB) target is conjugated to the surface of CMF to fabricate a tumor-specific nanozyme (PCMF). The core-shell nanostructure significantly avoids the oxidation and inactivation of copper-based nanozyme, promoting the antitumor activity of PCMF. The weak acid- and GSH-activated T1 and T2 relaxation rate of PCMF contributes to T1 and T2 dual contrast imaging at the tumor site. In addition, the PCMF disintegrates and produces some metal ions that possess Fenton catalytic activity (i.e., Cu+, Mn2+, and Fe2+) under TME. This process significantly depletes GSH, accelerates Fenton and Fenton-like reactions, enhances cellular reactive oxygen species (ROS) levels, and induces cancer cell apoptosis and ferroptosis. PCMF also exhibits photothermal functions, so it can be used in combined photothermal therapy, ferroptosis therapy, and chemodynamic therapy, improving anticancer activity. This work provides insights into the design of an exquisite nanostructure for high-sensitive and tumor-specific theranostics.
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Nanoestructuras , Neoplasias , Humanos , Medicina de Precisión , Cobre , Microambiente Tumoral , Imagen por Resonancia Magnética , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Peróxido de Hidrógeno , Línea Celular TumoralRESUMEN
Tumor hypoxia and systemic toxicity seriously affect the efficacy of photodynamic therapy (PDT) and are considered as the "Achilles' heel" of PDT. Herein, to combat such limitations, an intelligent orthogonal emissions LDNP@SiO2 -CaO2 and folic acid-polyethylene glycol-Ce6 nanodrug is rationally designed and fabricated not only for relieving the hypoxic tumor microenvironment (TME) to enhance PDT efficacy, but also for determining the optimal triggering time through second near-infrared (NIR-II) fluorescence imaging. The designed nanodrug continuously releases a large amount of O2 , H2 O2 , and Ca2+ ions when exposed to the acidic TME. Meanwhile, under downshifting NIR-II bioimaging guidance, chlorine e6 (Ce6) consumes oxygen to produce 1 O2 upon excitation of upconversion photon. Moreover, cytotoxic reactive oxygen species (ROS) and calcium overload can induce mitochondria injury and thus enhance the oxidative stress in tumor cells. As a result, the NIR-II bioimaging guided TME-responsive oxygen self-sufficient PDT nanosystem presents enhanced anti-tumor efficacy without obvious systemic toxicity. Thus, the fabricated nanodrug offers great potential for designing an accurate cancer theranostic system.
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Nanopartículas , Fotoquimioterapia , Fotoquimioterapia/métodos , Oxígeno , Dióxido de Silicio , Línea Celular Tumoral , Imagen Óptica , Fármacos Fotosensibilizantes/farmacología , Microambiente Tumoral , Nanopartículas/uso terapéuticoRESUMEN
Phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymers are considered to be the most promising holographic storage media due to their unique properties, such as high stability, a simple preparation process, low price, and volumetric shrinkage. This paper reviews the development process of PQ/PMMA photopolymers from inception to the present, summarizes the process, and looks at the development potential of PQ/PMMA in practical applications.
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Holografía , Polimetil MetacrilatoRESUMEN
BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.
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COVID-19 , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Pandemias , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
BACKGROUD: ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. The ZBTB7A has been largely linked to different kinds of tumors due to its diverse function. However, the value for ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear. METHODS: In our work, we assessed the importance of ZBTB7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co-expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZBTB7A and tumor immune invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CCK8, migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrial cancer cells. RESULTS: We found the ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expression of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers such as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Treg. Finally, we verified that ZBTB7A repressed E2F4 transcription and inhibited cells proliferation and migration. These results indicate that ZBTB7A may play a vital role in regulating immune cell infiltration in UCEC, and is a valuable prognostic marker. CONCLUSIONS: In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, plays a vital role in regulating immune cell infiltration, possesses diagnostic and prognostic values and attenuates E2F4 transcription and cell proliferation, migration in vitro.
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The current descriptive cross-sectional study aimed to explore the mediating role of perceived nursing work environment (PNWE) in the relationship between psychological capital (PsyCap) and perceived professional benefits among Chinese nurses. Participants (N = 351) working in two large general hospitals in Guangdong, China completed self-report questionnaires from March to May 2017. Linear regression analyses and structural equation modeling were performed to explore the mediating effect. PsyCap (particularly for hope and optimism) had a positive effect on perceived professional benefits, and PNWE was a mediator in this relationship among Chinese nurses. A good working environment can be regarded as a mediator variable, increasing staff's competence and sense of belonging to a team. For successful implementation, nurse managers should use effective strategies to increase nurses' confidence and hope while providing a comfortable work environment. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 38-47.].
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Personal de Enfermería/estadística & datos numéricos , Resiliencia Psicológica , Estrés Psicológico/psicología , Lugar de Trabajo/psicología , Adulto , China , Estudios Transversales , Femenino , Esperanza , Humanos , Masculino , Personal de Enfermería/psicología , Autoeficacia , Encuestas y CuestionariosRESUMEN
BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is used for treating unresectable hepatocellular carcinoma (HCC), but its efficacy still needs to be improved. Recombinant adenovirus p53 (rAd-p53) injection is a gene therapeutic agent that could improve the prognosis of HCC patients. This study aimed to evaluate the efficacy and safety of rAd-p53-based TACE for treating unresectable HCC. METHODS: Prospective analysis of patients who received rAd-p53-based TACE or TACE alone in Chongqing Cancer Institute from January 1, 2011 to December 31, 2012. The primary endpoint is overall survival. The secondary endpoints were progression-free survival, response rate, and safety. RESULTS: One hundred two patients were enrolled in this study. Forty-nine patients received the rAd-p53-based TACE, and 53 patients received TACE alone. The rAd-p53-based TACE treatment strategy improved the overall survival (hazard ratio: 0.58, 95% confidence interval: 0.35-0.96, P = 0.035), progression-free survival (hazard ratio: 0.60, 95% confidence interval: 0.37-0.97, P = 0.037), response rate (P = 0.047) compared with TACE monotherapy. The rAd-p53-based TACE treatment group caused more occurrences of fever than with TACE alone (P = 0.01). However, symptomatic treatment may solve this problem. CONCLUSIONS: rAd-p53-based TACE treatment strategy is effective and safe for treating unresectable HCC. Large-scale randomized clinical trials are needed to verify these results.
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Quimioembolización Terapéutica/métodos , Terapia Genética/métodos , Neoplasias Hepáticas/terapia , Proteína p53 Supresora de Tumor/administración & dosificación , Adenoviridae , Adulto , Anciano , Estudios de Cohortes , Terapia Combinada , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes/administración & dosificación , Tasa de SupervivenciaRESUMEN
BACKGROUND: Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients. DATA SOURCES: Randomized controlled trials comparing everolimus for de novo liver transplant in PubMed, the Cochrane Library, and ScienceDirect published up to March 31, 2014 were searched by two independent reviewers. Mean differences and 95% confidence interval (95% CI) for renal function, relative risk (RR) and 95% CI for treated biopsy-proven acute rejection (tBPAR), graft loss, death, neoplasms/tumor recurrence, and adverse events were collected. Meta-analyses were performed with RevMan version 5.10. RESULTS: A total of four randomized controlled trials covering 1119 cases were included. The meta-analyses revealed that compared with standard exposure of calcineurin inhibitors (CNIs), everolimus combined with reduced CNIs improved creatinine clearance (calculated with the Cockcroft-Gault formula) by 5.13 mL/min at one year (95% CI: 0.42-9.84; P=0.03), and decreased tBPAR (RR: 0.56; 95% CI: 0.35-0.90; P=0.02). Everolimus initiation with CNIs elimination improved glomerular filtration rate (GFR, measured with the modification of diet in renal disease formula) of 10.42 mL/min/1.73 m2 (95% CI: 3.44-17.41; P<0.01) one year after treatment, but increased tBPAR (RR: 1.71; 95% CI: 1.15-2.53; P<0.01). Everolimus decreased the risk of neoplasms/tumor recurrence after liver transplant (RR: 0.60; 95% CI: 0.34-1.03; P=0.06), but was associated with greater risk of adverse events which resulted in drug discontinuation (RR: 1.98; 95% CI: 1.49-2.64; P<0.01). CONCLUSIONS: Early introduction of everolimus combined with low-dose or no CNI in de novo liver transplant significantly improves renal function one year post treatment. Everolimus combined with low-dose CNI decreases the risk of tBPAR one year after liver transplant, but everolimus administered without CNIs increases tBPAR.
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Everolimus/uso terapéutico , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Neoplasias Hepáticas/prevención & control , Trasplante de Hígado , Recurrencia Local de Neoplasia/prevención & control , Insuficiencia Renal Crónica/fisiopatología , Inhibidores de la Calcineurina/administración & dosificación , Quimioterapia Combinada , Everolimus/efectos adversos , Rechazo de Injerto/patología , Humanos , Inmunosupresores/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To explore the correlation of pulse pressure(PP) and outcome in refractory septic shock patients. METHODS: A total of 68 patients with refractory septic shock consecutively admitted in our ICU from January 2012 to December 2012 were retrospectively studied. Hemodynamic data and arterial lactate concentration were collected at the time of admission and 24 hours after admission. The outcome of Day 28 post-diagnosis was also recorded. RESULTS: (1) Compared with the survivors, heart rate (HR) at 24 hours after admission was higher in non-survivors, while 24 h lactate clearance rate (rLac) was lower in them (P < 0.05). Other hemodynamic parameters showed no difference between the non-survivors and the survivors at 24 hours after admission, including central venous pressure (CVP), mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), PP, pulse pressure/heart rate (PP/HR), pulse pressure/mean arterial pressure (PP/MAP), pulse pressure/systolic pressure (PP/SBP), pulse pressure/diastolic pressure (PP/DBP), the value of SBP above MAP (SMP)and the value of DBP below MAP (MDP). (2)The mortality rate was higher in the patients with HR ≥ 100 b/min than those with HR<100 b/min, but without statistical significance (56.25% vs 36.11%, P = 0.096). Compared with the survivors, no matter with HR ≥ 100 b/min or HR<100 b/min, lactate (Lac) at the 24 hours after admission was higher in all the non-survivors (P < 0.05), while with lower rLac (P < 0.05). In those with HR ≥ 100 b/min, the following hemodynamic parameters were higher in the non-survivors than in the survivors, including PP, PP/HR, PP/MAP, PP/SBP, PP/DBP, SMP and MDP (all P values<0.05), while no statistical difference was observed in those with HR<100 b/min. (3) The mortality rate showed no statistical difference in those with MAP ≥ 85 mmHg (1 mmHg = 0.133 kPa) and with MAP < 85 mmHg (42.42% vs 48.57%, P = 0.611) . No matter MAP ≥ 85 mmHg or MAP < 85 mmHg, compared with the survivors, all the non-survivors had higher Lac at the 24 hours after admission (P < 0.05), while with lower rLac (P < 0.05). In those with MAP ≥ 85 mmHg, HR was higher in the non-survivors than the survivors (P < 0.05). In those with MAP < 85 mmHg, compared with the survivors, the non-survivors had higher PP, PP/MAP, PP/SBP, PP/DBP, SMP and MDP (P < 0.05), while with lower DBP (P < 0.05). CONCLUSION: PP is correlated with the outcome in refractory septic shock patients. When the HR and MAP differ, PP has different effect on the outcome and contributes more to the tissue perfusion and outcome in those with higher HR and lower MAP.
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Presión Sanguínea , Choque Séptico/diagnóstico , Choque Séptico/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The low photosensitivity of phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) severely limits its recording speed for holographic data storage. A high-performance holographic recording medium based on a unique combination of N-methylpyrrolidone (NMP) regulated PQ/PMMA has been developed. A NMP-PQ/PMMA photopolymer with high sensitivity, high diffraction efficiency and negligible volume shrinkage was successfully fabricated by tuning the composition of the PMMA matrix by varying the ratio of NMP to monomers. The photosensitivity is increased by 6.9 times (from 0.27 cm J-1 to 1.86 cm J-1), the diffraction efficiency is increased from 60% to > 80%, and volume shrinkage is decreased by a factor of 2 (from 0.4% to 0.2%). Further investigation revealed that the addition of NMP significantly reduced the molecular weight of PMMA and increased the amount of MMA residuals, while also improving the solubility of PQ molecules. More interestingly, for the first time, the NMP-PQ/PMMA material could record data information repeatedly at least 6 times. The present study elucidates that the introduction of NMP not only modulates the molecular weight of PMMA but also enables the residual monomer MMA to more easily combine with PQ to form a photoproduct for improved holographic performance.
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Phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymers are potential holographic storage media owing to their high-density storage capacities, low costs, high stability, and negligible shrinkage in volume holographic permanent memory. However, because of the limitations of the substrate, conventional Plexiglas materials do not exhibit a good performance in terms of photosensitivity and molding. In this study, the crosslinked structure of PMMA was modified by introducing a dendrimer monomer, pentaerythritol tetraacrylate (PETA), which increases the photosensitivity of the material 2 times (from ~0.58 cm/J to ~1.18 cm/J), and the diffraction efficiency is increased 1.6 times (from ~50% to ~80%). In addition, the modified material has a superior ability to mold compared to conventional materials. Moreover, the holographic performance enhancement was evaluated in conjunction with a quantum chemical analysis. The doping of PETA resulted in an overall decrease in the energy required for the reaction system of the material, and the activation energy decreased by ~0.5 KJ/mol in the photoreaction stage.
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The biotoxicity and chemotherapeutic resistance of cisplatin (CDDP) pose a challenge for tumor therapy. Practically, the change in the therapeutic response of tumor from resistance to sensitivity are impressive but challenging. To this end, we propose a strategy of "one stone, three birds" by designing a CuPt nanoalloy to simultaneously eliminate GSH, relieve hypoxia, and promote ROS production for effectively reversing the platinum (IV) (Pt(IV), (c,c,t-[Pt(NH3)2Cl2(OOCCH2CH2COOH)2)) resistance. Notably, the CuPt nanoalloy exhibits ternary catalytic capabilities including mimicking GSH oxidase, catalase and peroxidase. With the subsequent disguise of tumor cell membrane, the CuPt nanoalloy is conferred with homologous targeting ability, making it actively recognize tumor cells and then effectively internalized by tumor cells. Upon entering tumor cell, it gives rise to GSH depletion, hypoxia relief, and oxidative stress enhancement by catalyzing the reaction of GSH and H2O2, which mitigates the vicious milieu and ultimately reinforces the tumor response to Pt(IV) treatment. In vivo results prove that combination therapy of mCuPt and Pt(IV) realizes the most significant suppression on A549 cisplatin-resistant tumor. This study provides a potential strategy to design novel nanozyme for conquering resistant tumor.
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The problem of multi-detection multi-target tracking (MDMTT) using over-the-horizon radar in dense clutter environment is studied in this paper. The biggest challenge of MDMTT is the 3-dimensional multipath data association among measurements, detection models and targets. In particular, a lot of clutter measurements are generated in dense clutter environment, which increase the computational burden of 3-dimensional multipath data association greatly. A measurement based dimension descent association (DDA) algorithm is proposed to solve the 3-dimensional multipath data association, which decomposes the 3-dimensional multipath data association into two 2-dimensional data associations. The proposed algorithm can reduce the computational burden compared with the optimal 3-dimensional multipath data association and the computational complexity is analyzed. Besides, a time extension method is designed to detect the new-born targets that appear in the tracking scene, which is based on the sequential measurements. The convergence of the proposed measurement based DDA algorithm is analyzed. The estimation error can convergence to 0 as the number of Gaussian mixtures tends to infinity. The effectiveness and rapidity of the measurement based DDA algorithm are demonstrated by the comparative simulation with the previously proposed algorithms.
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The progress of critical care medicine in 2021 is still encouraging. The new international guideline for management of sepsis and septic shock came out after 4 years. Besides, a couple of preferable clinical evidences were released including restrictive blood transfusion strategy for patients with acute myocardial infarction, prevention of peripheral venous catheter infection, heparin inhalation and driving pressure setting in patients with acute respiratory distress syndrome (ARDS), lower oxygenation target for acute hypoxemic respiratory failure, low level positive end-expiratory pressure in non-ARDS patients with respiratory failure, light sedation or non-sedation strategy, biological phenotypes, as well machine learning in sepsis and ARDS. However, we also encounter negative results such as balanced solution during fluid resuscitation, hypothermia therapy after out-of-hospital cardiac arrest or traumatic brain injury, adrenomedullin-specific antibody adrecizumab therapy and coupled plasma filtration-adsorption (CPFA) therapy for patients with septic shock, extracorporeal carbon dioxide removal (ECCO2R) implementation in acute hypoxic respiratory failure, continuous infusion of hypertonic saline in patients with traumatic brain injury. Collectively, in the future, individualized diagnosis and management based on the principle of "wise choice" will become the daily practice scene for all intensivists.
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Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Choque Séptico , Cuidados Críticos , Humanos , Respiración con Presión Positiva , Síndrome de Dificultad Respiratoria/terapia , Choque Séptico/terapiaRESUMEN
Time-varying group formation-containment tracking problems for general linear multiagent systems with unknown control input are investigated. Agents are classified into tracking leaders, formation leaders, and followers and assigned in groups. Tracking leaders with unknown control inputs provide unpredictable trajectories as macroscopic moving references. Formation leaders accomplish desired subformations while following the trails of tracking leaders. At the same time, followers converge into different convex hulls spanned by formation leaders. First, formation-containment tracking protocols are designed with neighboring relative information and effects of unknown input of tracking leaders. Then, the design of group division is analyzed by adjusting the properties in Laplacian matrices, which represent interaction relationships. An algorithm to determine the parameters in control protocols is proposed, and the formation tracking feasible constraint is presented. Next, it is proved that the general linear multiagent system can achieve time-varying group formation-containment control effectively with errors uniformly asymptotically converging to zero under designed protocols. Finally, a numerical simulation is given to verify the effectiveness of obtained theoretical results.
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We explored the catalytic activity and magnetic resonance imaging (MRI) capacity of Cu-doped ultrasmall iron oxides with different doping ratios. Then, we screened a highly efficient ultrasmall active catalyst (UAC). Subsequently, a biodegradable magnetic nanoliposome was developed for multimodal cancer theranostics through pH-sensitive liposome coating of these UACs. Upon entering the body, the magnetic nanoliposomes significantly prolonged the metabolic time of UACs and promoted their accumulation in tumors. Then, the strong photothermal (PT) effect of the magnetic nanoliposome quickly ablated the tumor, showing promising PT therapy. Upon entering tumor cells, the magnetic nanoliposome rapidly degraded into many UACs and released chemotherapeutic drugs, contributing to chemotherapy. In addition, UACs not only catalyzed Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also inhibited the synthesis of endogenous GSH by inactivating glutamyl cysteine ligase, contributing to cancer ferroptosis. Furthermore, the assembly-dissociation process of UACs showed the function of magnetic relaxation switches, significantly enhancing tumor MRI signal change, achieving a more accurate diagnosis of the tumor. Therefore, this magnetic nanoliposome splits into many UACs upon drug release and regulates the tumor microenvironment to overproduce ROS for enhanced synergistic tumor theranostics, which provides a strategy for developing next-generation magnetic catalysts with biodegradability and multimodal antitumor theranostics.
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Nanopartículas , Microambiente Tumoral , Línea Celular Tumoral , Imagen por Resonancia Magnética , Terapia Fototérmica , Especies Reactivas de Oxígeno/metabolismo , Nanomedicina Teranóstica/métodosRESUMEN
A self-preservation Pt(IV) nanoplatform, amorphous ferric oxide-coating selenium core-shell nanoparticles (iAIO@NSe-Pt), was developed for H2O2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis. Upon entry into the blood, the ferric oxide shell effectively blocked the contact Pt(IV) prodrug with reduced molecules, then avoided the inactivation of the Pt(IV) prodrug and increased its accumulation in the tumor. After entering cancer cells, iAIO@NSe-Pt caused a series of cascade reactions: (1) AIO on the surface of iAIO@NSe-Pt quickly dissolved, released an abundance of Fe(II) because of the weakly acidic tumor microenvironment, and then catalyzed cellular H2O2 into highly toxic ËOH, resulting in cellular H2O2 deficiency and cell ferroptosis. (2) The platinum(IV) prodrugs were exposed and quickly reduced to highly toxic Pt(II) by depleting GSH. This process inactivated GPX4, promoted ROS accumulation, and further accelerated ferroptosis. In addition, the generated Pt(II) quickly inhibited DNA replication, achieving effective apoptotic cell death. Meanwhile, Pt(II) inactivated SOD1, which blocked the synthesis of cellular H2O2 and accelerated ROS (superoxide anion radical) accumulation. (3) The deficiency of cellular H2O2 significantly inhibited the expression of vascular endothelial growth factor-A (VEGF-A), blocking tumor angiogenesis and then improving the anticancer effect. (4) After such a cascade reaction, the exposed NSe successively disrupted mitochondrial respiration and inhibited cancer angiogenesis, further inducing cancer cell death. Collectively, our functional and mechanical investigation suggested that iAIO@NSe-Pt exhibits excellent tumor targeting, biocompatibility and anti-tumor efficiency in vitro and in vivo, and provides a novel example of a self-preservation Pt(IV) nanoplatform for H2O2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis, showing great promise for future clinical use.
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Ferroptosis , Nanopartículas , Neoplasias , Profármacos , Selenio , Apoptosis , Línea Celular Tumoral , Compuestos Férricos , Humanos , Peróxido de Hidrógeno/uso terapéutico , Neoplasias/tratamiento farmacológico , Profármacos/farmacología , Profármacos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral , Factor A de Crecimiento Endotelial VascularRESUMEN
Fully adaptive practical time-varying output formation tracking issues of high-order nonlinear stochastic multiagent systems with multiple leaders are researched, where the adaptive fuzzy-logic system (FLS) is introduced for estimating the mismatched integrated uncertain items. Distinctive with former results, stochastic noise is considered in the dynamics, and the followers are required for achieving the time-varying output formation tracking in probability of the convex combination of the leaders' outputs. First, a fully adaptive practical time-varying output formation tracking protocol is put forward, which only utilizes the neighboring relative information, and the global interaction topology information is not used. Besides, the designed protocol employs the adaptive FLSs to estimate the mismatched uncertainties of the followers and the leaders, and the uncertain boundary functions of the stochastic noise. Then, the design process of control protocol and parameter adaptive update law is summarized within four steps in an algorithm. Third, the stability and the properties of the proposed protocol and algorithm are analyzed by employing the Lyapunov theories and stochastic stability theories. Finally, numerical simulation results illustrate the effectiveness of achieved protocol and algorithm.
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This paper addresses the distributed state estimation problem for a class of discrete nonlinear system over sensor networks subject to unknown correlated measurement noises. Firstly, under the condition of network connectivity, a novel communication protocol is developed to ensure every sensor node can gather the information distributed throughout the network within finite communication time. Then a fully distributed estimator is designed by periodically fusing the local information and neighbor's information according to the covariance intersection fusion strategy. Theoretically, it is proved that the distributed estimator in each sensor node is stable with the exponentially bounded estimation error in mean square. Finally, some numerous simulations are performed to illustrate the practical effectiveness and superiority of the proposed state estimator.