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Tumor cells increase glutamate release through the cystine/glutamate transporter cystine-glutamate exchange (xCT) to balance oxidative homeostasis in tumor cells and promote tumor progression. Although clinical studies have shown the potential of targeting programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling in melanoma, response rates are low. However, it remains unclear how glutamate metabolism affects anti-PD-1/PD-L1 treatment efficacy in melanoma. Here, we demonstrated that although inhibition of xCT either by pharmacological inhibitor (sulfasalazine [SAS]), approved by US Food and Drug Administration (FDA) for inflammatory diseases, or genetic knockdown induced reactive oxygen species (ROS)-related death in melanoma cells, inhibition of xCT significantly reduced the efficacy of anti-PD-1/PD-L1 immune checkpoint blockade through upregulating PD-L1 expression via the transcription factors IRF4/EGR1, as a consequence, exosomes carrying relatively large amounts of PD-L1 secreted from melanoma cells resulted in M2 macrophage polarization and reduced the efficacy of anti-PD-1/PD-L1 therapy in melanoma. Taken together, our results reveal that inhibition of xCT by SAS is a promising therapeutic strategy for melanoma; on the other hand, SAS treatment blunted the efficacy of anti-PD-1/PD-L1 via exosomal PD-L1-induced macrophage M2 polarization and eventually induced anti-PD-1/PD-L1 therapy resistance.

Pattern formation and synchronization stability in the network are dependent on the local kinetics, connection type, and property of coupling channel. The coupling channels is often controlled to reach synchronization and pattern selection. From dynamical viewpoint, all the bifurcation parameters and coupling channels can be adjusted to get desired patterns and behaviors. However, the physical parameters for most of the electronic components are fixed even some of them can be adjusted in slight range. Thermistor is a kind of nonlinear electronic components, and its resistance is dependent on the temperature completely. It can be used to detect the fluctuation of environment temperature by building nonlinear circuits composed of thermistors. The coupling channel can be adjusted by the temperature when the thermistors are used to couple two or more nonlinear circuits. In this paper, the thermistors are used to couple Chua circuits in a square array with regular connection between adjacent nodes in the network. Gradient distribution of temperature on the network can induce diversity in the coupling intensity in the network because the channel resistances of the coupling thermistors are influenced by the heterogeneous distribution of temperature. In fact, the nodes close to the heat source have higher temperature and they are coupled with stronger intensity because of lower resistances for the coupling thermistors. Perfect target waves can be induced and propagated in the network by taming the temperature for coupling channels. Furthermore, statistical synchronization factor is calculated to estimate the synchronization stability and wave propagation in the network. These results suggested that physical components with adjustable parameters can be used in practical control of nonlinear systems.

Temperature has distinct impact on the activation of neural activities by adjusting the excitability and channel conductance. Some biological neurons can percept slight changes of temperature and then appropriate firing modes are induced under different temperatures. Indeed, the temperature-dependent property can be described by using thermistors, which can be included to build functional neural circuits. Therefore, any changes in the resistance of the thermistor can regulate the branch current and also the output voltage completely. In the paper, thermistors are connected to the FitzHugh-Nagumo neural circuit driven by a voltage source, and a thermosensitive neuron oscillator is obtained by applying scale transformation for the physical variables and parameters in the neural circuit. The thermistor is connected to different branch circuits to enhance the sensitivity to changes of temperature. It is confirmed that the neural activities can present distinct mode transition from spiking to bursting and chaotic states. In particular, the external stimulus becomes dependent on temperature when the thermistor is connected to the external voltage source. Stochastic resonance and multiple modes are detected when additive Gaussian white noise is applied on an isolated neuron controlled by temperature. Therefore, a sensitive sensor of temperature is obtained, and this feasible neuron model can be effective to investigate the collective behaviors of neural networks in the presence of time-varying temperature. Also, the Hamilton energy is estimated to predict the mode selection and effect of noise.

Phototube can capture and transmit external illumination with high frequency into photocurrent in the nonlinear circuit, which can be tamed to produce the main dynamical properties of biological neurons. In fact, the involvement of functional electronic components can enhance the biophysical function of artificial neural circuits. In this paper, a photocell is connected to FitzHugh-Nagumo neural circuits, which can be excited by the photocurrent generated from the photocell. Furthermore, a memristor is proposed to couple two light-dependent neural circuits and the synchronization stability is investigated on the coupled dynamical systems by using standard scale transformation on the physical variables and parameters. It is found that phase synchronization and complete synchronization can be obtained by regulating the coupling channel connected by the memristor. The propagation and pumping of field energy are also calculated to predict the occurrence of synchronization.

The effect of pre-ageing temperature and retrogression heating rate variations on the mechanical properties and electrical conductivity of the RRA treated AA7055 has been investigated. The microstructures under various RRA treated samples are discussed in detail. The results reveal that, near peak aged state plus slow retrogression heating is more applicable for industrial processing. Under the pre-ageing at 105 °C/24 h and a slow retrogression heating rate of 3 °C/min condition, RRA-treated samples possess a better combination of both strength and electrical conductivity than the T6 or T73 states.