Human orbitofrontal cortex signals decision outcomes to sensory cortex during behavioral adaptations

The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior

Phase constitution of the noble metal thin-film complex solid solution system Ag-Ir-Pd-Pt-Ru in dependence of elemental compositions and annealing temperatures

Multiple-principal element alloys hold great promise for multifunctional material discovery (e.g., for novel electrocatalysts based on complex solid solutions) in a virtually unlimited compositional space. Here, the phase constitution of the noble metal system Ag-Ir-Pd-Pt-Ru was investigated over a large compositional range in the quinary composition space and for different annealing temperatures from 600 to 900 °C using thin-film materials libraries. Composition-dependent X-ray diffraction mapping of the as-deposited thin-film materials library indicates different phases being present across the composition space (face-centered cubic (fcc), hexagonal close packed (hcp) and mixed fcc + hcp), which are strongly dependent on the Ru content. In general, low Ru contents promote the fcc phase, whereas high Ru contents favor the formation of an hcp solid-solution phase. Furthermore, a temperature-induced phase transformation study was carried out for a selected measurement area of fcc-$Ag_{5}Ir_{8}Pd_{56}Pt_{8}Ru_{23}$. With increasing temperature, the initial fcc phase transforms to an intermediate C14-type Laves phase at 360 °C, and then to hcp when the temperature reaches 510 °C. The formation and disappearance of the hexagonal Laves phase, which covers a wide temperature range, plays a crucial role of bridging the fcc to hcp phase transition. The obtained composition, phase and temperature data are transformed into phase maps which could be used to guide theoretical studies and lay a basis for tuning the functional properties of these materials

Differences in discounting behavior and brain responses for food and money reward

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher $\it k$ values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices

Encapsulation of platinum prodrugs into PC7A polymeric nanoparticles combined with immune checkpoint inhibitors for therapeutically enhanced multimodal chemotherapy and immunotherapy by activation of the STING pathway

Tumor immunotherapy has emerged as one of the most promising therapeutic methods to treat cancer. Despite its clinical application, the immunosuppressive tumor microenvironment compromises the therapeutic efficiency of this technique. To overcome this limitation, many research efforts have been devoted to the development of agents that reprogram the immunosuppressive tumor microenvironment through novel mechanisms. Over the last decade, compounds that intervene through the immunogenic stimulator of interferon genes (STING) pathway have emerged with potential for clinical development. Herein, the encapsulation of chemotherapeutic platinum complexes with a polymer with a cyclic seven-membered ring (PC7A)-based polymer into pH-responsive nanoparticles for multimodal therapeutically enhanced chemotherapy and immunotherapy is presented. This study represents the first nanomaterial with a dual activation mechanism of the STING pathway through DNA fragmentation as well as PC7A binding. The combination of these nanoparticles with immune checkpoint inhibitors demonstrates to nearly fully eradicate a colorectal tumor inside the mouse model by chemotherapy and immunotherapy using the STING pathway