No abstract

Layered BSA-MoS2 nanoflowers are designed and synthesized as excellent microwave (MW) hyperthermia susceptive agents for in vivo cancer therapy via MW irradiation at 1.8 W, 450 MHz, which shows great potential for green tumor thermotherapy.

This study demonstrates how model bias can adversely affect the quality assessment of an ensemble prediction system (EPS) by verification metrics. A regional EPS [Global and Regional Assimilation and Prediction Enhanced System-Regional Ensemble Prediction System (GRAPES-REPS)] was verified over a period of one month over China. Three variables (500-hPa and 2-m temperatures, and 250-hPa wind) are selected to represent “strong” and “weak” bias situations. Ensemble spread and probabilistic forecasts are compared before and after a bias correction. The results show that the conclusions drawn from ensemble verification about the EPS are dramatically different with or without model bias. This is true for both ensemble spread and probabilistic forecasts. The GRAPES-REPS is severely underdispersive before the bias correction but becomes calibrated afterward, although the improvement in the spread’s spatial structure is much less; the spread–skill relation is also improved. The probabilities become much sharper and almost perfectly reliable after the bias is removed. Therefore, it is necessary to remove forecast biases before an EPS can be accurately evaluated since an EPS deals only with random error but not systematic error. Only when an EPS has no or little forecast bias, can ensemble verification metrics reliably reveal the true quality of an EPS without removing forecast bias first. An implication is that EPS developers should not be expected to introduce methods to dramatically increase ensemble spread (either by perturbation method or statistical calibration) to achieve reliability. Instead, the preferred solution is to reduce model bias through prediction system developments and to focus on the quality of spread (not the quantity of spread). Forecast products should also be produced from the debiased but not the raw ensemble.

Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO nanoparticles (BB-ZrO NPs). The microwave energy conversion efficiency of BB-ZrO NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 μM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO + MW group during the therapy of subcutaneous tumors even on the 42 day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and tri-stimuli-responsive chemotherapy, which may have potential applications in clinic.