Co-delivery of resveratrol and docetaxel via polymeric micelles to improve the treatment of drug-resistant tumors

Co-delivery of anti-cancer drugs is promising to improve the efficacy of cancer treatment. This study was aiming to investigate the potential of concurrent delivery of resveratrol (RES) and docetaxel (DTX) via polymeric nanocarriers to treat breast cancer. To this end, methoxyl poly(ethylene glycol)-poly(d,l-lactide) copolymer (mPEG-PDLA) was prepared and characterized using FTIR and 1H NMR, and their molecular weights were determined by GPC. Isobologram analysis and combination index calculation were performed to find the optimal ratio between RES and DTX to against human breast adenocarcinoma cell line (MCF-7 cells). Subsequently, RES and DTX were loaded in the mPEG-PDLA micelles simultaneously, and the morphology, particle size distribution, in vitro release, pharmacokinetic profiles, as well as cytotoxicity to the MCF-7 cells were characterized. IC50 of RES and DTX in MCF-7 cells were determined to be 23.0 µg/ml and 10.4 µg/ml, respectively, while a lower IC50 of 4.8 µg/ml of the combination of RES and DTX was obtained. The combination of RES and DTX at a ratio of 1:1 (w/w) generated stronger synergistic effect than other ratios in the MCF-7 cells. RES and DTX loaded mPEG-PDLA micelles exhibited prolonged release profiles, and enhanced cytotoxicity in vitro against MCF-7 cells. The AUC(0→t) of DTX and RES in mPEG-PDLA micelles after i.v. administration to rats were 3.0-fold and 1.6-fold higher than that of i.v. injections of the individual drugs. These findings indicated that the co-delivery of RES and DTX using mPEG-PDLA micelles could have better treatment of tumors. Keywords: Resveratrol, Docetaxel, Methoxyl poly(ethylene glycol)-poly(d,l-lactide) copolymer (mPEG-PDLA), Micelles, Drug resistance tumo

Resting-state brain activity predicts selective attention deficits during hyperthermia exposure

Purpose Environmental hyperthermia exerts detrimental effect on attention performance that might increase the probability of accidents for high risk occupation. Previously, we reported aberrant activations and selective attention deficits under task performing during hyperthermia. However, whether resting-state baseline during hyperthermia would contribute to the reported selective attention deficits remains unclear. Materials and methods Here, we investigated the resting-state activity within two attention subsystems named dorsal attention network (DAN) and ventral attention network (VAN) using the conjoint analysis of functional connectivity (FC) and regional cerebral blood flow (CBF). Blood oxygenation level dependent (BOLD) and 3 D arterial spin labeling data were obtained from 25 healthy male participants under two simulated thermal conditions: normothermic (25 °C for 1 h) and hyperthermic condition (50 °C for 1 h). Results Paired comparisons on the FC and CBF showed decreased activity in the bilateral frontal eye field (FEF) and intraparietal sulcus (IPS) in the DAN but increased activity in the ventral frontal cortex (VFC) in the VAN. The CBF-FC correlation analysis further confirmed decreased CBF-FC coupling in the bilateral FEF in the DAN and increased coupling in the VFC in the VAN. Additionally, the left IPS and FEF in the DAN showed altered CBF per unit functional connectivity in the CBF/FC ratio analysis. Multiple regression analysis revealed that the selectively altered performances were predicted by alterations of the multiple metrics within the DAN and VAN. Conclusions These findings suggested that altered resting-state brain activity within the attention networks might provide potential neural basis of the selective deficits for different cognitive-demand attention tasks under hyperthermia

Suppression of Fading Noise in Satellite-Mediated Continuous-Variable Quantum Key Distribution via Clusterization

The satellite-mediated continuous-variable quantum key distribution (CV-QKD) protocol, which relies on off-the-shelf telecommunication components, has the potential for a global quantum communication network with all-day operation. However, the transmittance fluctuation of satellite-mediated links leads to the arriving quantum state showing non-Gaussian property, introducing extra fading noise in security analysis and limiting the secret key rate of the protocol. Here, we consider the clusterization method for data post-processing to suppress the fading noise in both downlink and uplink scenarios, where the measurement data are divided into several clusters, and we perform security analysis separately. In particular, we set the optimal upper and lower bounds of each cluster in terms of the probability distribution of transmittance (PDT), while finding an optimal cluster number for the trade-off between fading noise and the composable finite-size effect. Numerical analysis shows that the proposed method can improve the composable finite-size rate when the fading noise is large enough, even with only two clusters. Moreover, a high-speed CV-QKD system with a higher frequency of signal preparation and detection can extend the proposed method to work in the case of lower fading noise

Research on the Development of Rural E-commerce in China

At present, rural e-commerce is characterized by obvious improvement in market prospect, development scale and development momentum, but there are also some problems, such as farmers' low acceptance of e-commerce, lack of promotion and training of rural e-commerce, and lack of rural e-commerce talents. Based on these problems, the government needs to increase financial support for rural e-commerce, improve the distribution logistics system, and strengthen the training of rural e-commerce personnel to promote the sustainable development of rural e-commerce

Reflections on the High-quality Development of Rural Areas in Guangshan County, Xinyang City

The problems faced by the development of Guangshan County were analyzed from the aspects of rural management talents, industrial structure, e-commerce development, and farmers' ideology, and corresponding solutions were proposed to improve the development speed of rural areas in the county and promote the high-quality development of the county as a whole

Optimization of the Fermentative Production of Rhizomucor miehei Lipase in Aspergillus oryzae by Controlling Morphology

Morphology plays an important role in the fermentation bioprocess of filamentous fungi. In this study, we investigated the controlling strategies of morphology that improved the efficiency of Rhizomucor miehei lipase (RML) production using a high-yield Aspergillus oryzae. First, the inoculated spore concentrations were optimized in seed culture, and the RML activity increased by 43.4% with the well-controlled mycelium pellets in both ideal sizes and concentrations. Then, the initial nitrogen source and agitation strategies were optimized to regulate the morphology of Aspergillus oryzae in a 5 L bioreactor, and the established stable fermentation system increased the RML activity to 232.0 U/mL, combined with an increase in total RML activity from 98,080 U to 487,179 U. Furthermore, the optimized fermentation strategy was verified by a high-yield Aspergillus oryzae and achieved an additional improvement of RML activity, up to 320.0 U/mL. Moreover, this optimized fermentation bioprocess was successfully scaled up to a 50 L bioreactor, and the RML activity reached 550.0 U/mL. This work has established a stable precision fermentation bioprocess for RML production by A. oryzae in bioreactors, and the controlling strategy developed in this study could potentially be extended to an industrial scale for RML production with high efficiency

Research on the Development of Rural E-commerce in China

At present, rural e-commerce is characterized by obvious improvement in market prospect, development scale and development momentum, but there are also some problems, such as farmers' low acceptance of e-commerce, lack of promotion and training of rural e-commerce, and lack of rural e-commerce talents. Based on these problems, the government needs to increase financial support for rural e-commerce, improve the distribution logistics system, and strengthen the training of rural e-commerce personnel to promote the sustainable development of rural e-commerce

A temperature-regulated circuit for feeding behavior

Feeding behavior is modulated by ambient temperature, as lower temperatures increase the necessity for energy intake and vice versa. Here the authors identify neuronal pathways that control feeding in a temperature-dependent manner

Magnaporthe oryzae effector MoSPAB1 directly activates rice Bsr-d1 expression to facilitate pathogenesis

Abstract Fungal pathogens typically use secreted effector proteins to suppress host immune activators to facilitate invasion. However, there is rarely evidence supporting the idea that fungal secretory proteins contribute to pathogenesis by transactivating host genes that suppress defense. We previously found that pathogen Magnaporthe oryzae induces rice Bsr-d1 to facilitate infection and hypothesized that a fungal effector mediates this induction. Here, we report that MoSPAB1 secreted by M. oryzae directly binds to the Bsr-d1 promoter to induce its expression, facilitating pathogenesis. Amino acids 103-123 of MoSPAB1 are required for its binding to the Bsr-d1 promoter. Both MoSPAB1 and rice MYBS1 compete for binding to the Bsr-d1 promoter to regulate Bsr-d1 expression. Furthermore, MoSPAB1 homologues are highly conserved among fungi. In particular, Colletotrichum fructicola CfSPAB1 and Colletotrichum sublineola CsSPAB1 activate kiwifruit AcBsr-d1 and sorghum SbBsr-d1 respectively, to facilitate pathogenesis. Taken together, our findings reveal a conserved module that may be widely utilized by fungi to enhance pathogenesis