RESUMO
In this paper, we propose a system for enhancing the RF output power of the photodetector, especially the power of fundamental tune and second-order harmonic, by feeding back part of the RF signal through an electrical feedback circuit. As a result of bias modulation and opto-electric mixing, the RF output power can be effectively enhanced. The structure of uni-traveling carrier photodetector (UTC-PD) is employed in this work. With the RF enhancement system, the power of fundamental tune and second-order harmonic improve by 6.4â dB and 9.9â dB respectively, under the condition of 26 dBm input optical power, 3â V bias voltage, and 14â GHz input optical signal. Further, it was observed that third-order harmonic appeared under the influence of this system.
RESUMO
BACKGROUND: Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. RESULTS: Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. CONCLUSIONS: Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma.
Assuntos
Ferroptose , Melanoma , Nanopartículas , Fotoquimioterapia , Camundongos , Animais , Fotoquimioterapia/métodos , Melanoma/tratamento farmacológico , Carbono/farmacologia , Carbono/química , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Imageamento por Ressonância Magnética , Nanopartículas/químicaRESUMO
Avoiding ischemic necrosis after flap transplantation remains a significant clinical challenge. Developing an effective pretreatment method to promote flap survival postoperatively is crucial. Cobalt chloride (CoCl2) can increase cell tolerance to ischemia and hypoxia condition by stimulating hypoxia-inducible factor-1 (HIF-1) expression. However, the considerable toxic effects severely limit the clinical application of CoCl2. In this study, cobalt-based metal-organic frameworks (Co-MOF) encapsulated in a microneedle patch (Co-MOF@MN) was developed to facilitate the transdermal sustained release of Co2+ for rapid, minimally invasive rapid pretreatment of flap transplantation. The MN patch was composed of a fully methanol-based two-component cross-linked polymer formula, with a pyramid structure and high mechanical strength, which satisfied the purpose of penetrating the skin stratum corneum of rat back to achieve subcutaneous vascular area administration. Benefiting from the water-triggered disintegration of Co-MOF and the transdermal delivery via the MN patch, preoperative damage and side effects were effectively mitigated. Moreover, in both the oxygen-glucose deprivation/recovery (OGD/R) cell model and the rat dorsal perforator flap model, Co-MOF@MN activated the HIF-1α pathway and its associated downstream proteins, which reduced reperfusion oxidative damage, improved blood supply in choke areas, and increased flap survival rates post-transplantation. This preprotection strategy, combining MOF nanoparticles and the MN patch, meets the clinical demands for trauma minimization and uniform administration in flap transplantation. STATEMENT OF SIGNIFICANCE: Cobalt chloride (CoCl2) can stimulate the expression of hypoxia-inducible factor (HIF-1) and improve the tolerance of cells to ischemia and hypoxia conditions. However, the toxicity and narrow therapeutic window of CoCl2 severely limit its clinical application. Herein, we explored the role of Co-MOF as a biocompatible nanocage for sustained release of Co2+, showing the protective effect on vascular endothelial cells in the stress model of oxygen-glucose deprivation. To fit the clinical needs of minimal trauma in flap transplantation, a Co-MOF@MN system was developed to achieve local transdermal delivery at the choke area, significantly improving blood supply opening and flap survival rate. This strategy of two-step delivery of Co2+ realized the enhancement of biological functions while ensuring the biosafety.
Assuntos
Cobalto , Estruturas Metalorgânicas , Retalhos Cirúrgicos , Animais , Humanos , Masculino , Ratos , Cobalto/química , Cobalto/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia/patologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Necrose , Ratos Sprague-Dawley , Adesivo TransdérmicoRESUMO
The Southern Ocean is the primary region for the uptake of anthropogenic carbon dioxide (CO2) and is, therefore, crucial for Earth's climate. However, the Southern Ocean CO2 flux estimates reveal substantial uncertainties and lack direct validation. Using seven independent and directly measured air-sea CO2 flux datasets, we identify a 25% stronger CO2 uptake in the Southern Ocean than shipboard dataset-based flux estimates. Accounting for upper ocean temperature gradients and insufficient temporal resolution of flux products can bridge this flux gap. The gas transfer velocity parameterization is not the main reason for the flux disagreement. The profiling float data-based flux products and biogeochemistry models considerably underestimate the observed CO2 uptake, which may be due to the lack of representation of small-scale high-flux events. Our study suggests that the Southern Ocean may take up more CO2 than previously recognized, and that temperature corrections should be considered, and a higher resolution is needed in data-based bulk flux estimates.