Graphene quantum dots (GQDs) have gained attention in the bioimaging community due to their biocompatibility and enhanced imaging depth in the near infra-red (NIR). Developing and optimizing a facile synthesis method of biocompatible NIR fluorescent GQDs from a variety of precursors remains, therefore, a critical task. Herein, we synthesized various GQD structures capable of fluorescing in the NIR via facile bottom-up pyrolysis of precursor materials (ascorbic acid, chitosan, citric acid, dextran, glucose, glucosamine hydrochloride, hyaluronic acid, l-glutamic acid, polyethylene glycol (PEG), sodium cholate, or sodium citrate). All synthesized GQD structures exhibit remarkable biocompatibility at concentrations of up to 1 mg/mL evaluated by an MTT assay which makes them suitable for a variety of therapeutic applications. All 11 GQD structures are successfully tracked by their NIR fluorescence in vitro bioimaging while exhibiting effective cellular internalization maximized at 12 hours in HEK293 cell line. This work provides a unique comprehensive study exploring a scalable and cost-effective process to synthesize NIR-emissive highly biocompatible GQDs from 11 precursor materials, while theoretically describing their optical properties. Due to their exceptional biocompatibility and photostable NIR emission, GQD structures developed here are expected to become prominent candidates for future clinical fluorescence imaging applications.

Modulating the Interferon Response to Enhance Oncolytic Virotherapy in Cancer Treatment
Anushka Velala, Hana Dobrovolny Ph.D
TCU Department of Physics, Fort Worth, TX
Background: Oncolytic viruses (OVs) are a promising immunotherapeutic strategy that can selectively target and lyse cancer cells while stimulating an anti-tumor immune response. However, their efficiency is often limited by the interferon (IFN) response, which acts as a key antiviral defense mechanism in host cells. Understanding the interplay between oncolytic viruses and IFN signaling is crucial for optimizing viral-based cancer therapies that have potential of success.
Hypothesis/Objective: This study aims to investigate how oncolytic viruses interact with the IFN response in a simulated tumor microenvironment. We hypothesize that higher values of variation in the IFN modulation can significantly negatively affect viral replication and therapeutic oncolytic efficacy.
Study Design and Research Methods: An analysis was conducted using a mathematical model with systems of differential equations. This model encompasses factors such as tumor growth, oncolytic infection dynamics, viral production and clearance, and the IFN-mediated immune response. Furthermore, sensitivity analysis was conducted to assess the influence of key parameters, including viral production rate, infection rate, and IFN clearance, on the treatment outcomes.
Results: Various simulations indicate that higher IFN levels correlate with reduced viral spread, leading to diminished oncolytic activity. However, parameter variations suggest that therapeutic efficacy can be optimized by adjusting certain parameters to mitigate excessive IFN responses. For instance, higher values of IFN efficacy are correlated with stronger IFN-mediated suppression of viral production, leading to lower sustained viral loads, while lower IFN efficacy levels allow for prolonged high viral replication. Similarly, IFN clearance rate affects how long IFN-induced killing of infected cells and uninfected cells persists, which can modulate the viral load over time. The most effective interferon response is a low-level response with low IFN clearance and high values of IFN efficacy, coupled with higher values of IFN-induced killing of uninfected cancer cells.
Conclusions: These findings underscore the role of the IFN response in modulating OV therapy and suggest that targeted suppression of IFN signaling could enhance OV efficacy in resistant tumors. This research provides insights for optimizing oncolytic virotherapy and improving clinical outcomes in cancer treatment, given the rising prominence of immunotherapy.

Frustrative nonreward (FNR), an adverse reaction brought on by unexpected reward reductions or omissions, can be induced by a downshift in the quantity or quality of the reward. The consummatory successive negative contrast (cSNC) task is a well-known paradigm for studying FNR. cSNC involves monitoring the behavioral reaction to a lower reward (downshift) after exposure to a larger or better incentive. It supports the idea that an acceptable but less preferred reward will be rejected in a situation that is associated with a better and more desirable reward. The intensity of FNR depends, among other things, on the strength of the expectation of the large reward. We assumed that overtraining would enhance reward expectancy such that a reward downshift would lead to a stronger cSNC effect than that observed under regular training conditions. This would support the hypothesis that behavior (licking for sucrose) was guided by reward expectancies—an action. But overtraining often leads to habitual behavior that depends on eliciting stimuli, rather than reward expectancies. A failure to show the cSNC effect after overtraining would be consistent with the hypothesis that behavior had become automatic—a habit. Our experiment was designed to test whether overtraining in the cSNC task would result in behavior becoming either an action or a habit. In the experiment, 47 rats were exposed to different concentrations of sucrose, 32%, 16%, or 4%, and 2 training periods, overtraining for 30 sessions and regular training for 10 sessions. Animals exposed to 32% and 16% sucrose were randomly assigned to two groups depending on the amount of training they received before the downshift, either 30 (overtraining) or 10 sessions (regular training). These animals were given access to 4% sucrose after their designated training period. An unshifted control group received only access to 4% sucrose throughout training. The data obtained after 10 vs. 30 sessions of training were compared to the unshifted controls. The results showed that overtraining enhanced the cSNC effect relative to regular training, suggesting that licking was an action guided by the expectation of the current reward, rather than a habit. These results suggest that FNR induced by reward downshifts overcomes the development of a habit even after prolonged training.

Recent discussions surrounding law enforcement have highlighted varying opinions on the ability of police officers to respond effectively to mental health-related incidents. Given that 20% of police calls involve mental health or substance abuse issues, it is crucial that the general population is confident about the role of police as mental health interventionalists. The current study assessed DFW residents’ (N = 64) perceptions of the police’s ability to intervene in mental health crises utilizing in-person and online 7-point Likert scale surveys (where 1 = disagree strongly and 7 = agree strongly). Survey results showed that confidence in police’s ability to handle mental health crises increases with age, p = .04. Older participants expressed greater trust, while younger respondents were more skeptical. No significant differences were found in gender, race, ethnicity, or socioeconomic status, highlighting a generational divide in public trust. These results suggest that there is potential for improving younger individuals’ attitudes towards police intervention.

Rats use many cues when navigating to food, shelter, or a mate. The use of visual cues (e.g., landmarks) has been reported in many species. In rats, these cues include those around their start position, the experimenter, as well as landmarks located in (intramaze) or around (extramaze) the search space. In the current experiment, rats were placed into a start box with a transparent door and released onto an open field. We examined whether rats were able to discriminate between two different intramaze landmarks (wooden figurines; A and B) from the start box. Landmark A trials were reinforced with a Froot Loop© hidden in a cup behind the landmark (A+), but no Froot Loop was present on Landmark B (B-) trials or on C- trials with no landmark. Latency to the goal cup was measured and revealed no differences between the three trial types. The procedure was modified to include two response locations (to the left and right of the landmark). A+ and B+ trial types were reinforced at different cups. There was no difference in accuracy for searching the correct cup first. The use of non-visual cues, the discriminability of the landmarks, and the response cost of search will be discussed.