Evolution of cooperation on reinforcement-learning driven-adaptive networks.

Complex networks are widespread in real-world environments across diverse domains. Real-world networks tend to form spontaneously through interactions between individual agents. Inspired by this, we design an evolutionary game model in which agents participate in a prisoner's dilemma game (PDG) with their neighboring agents. Agents can autonomously modify their connections with neighbors using reinforcement learning to avoid unfavorable environments. Interestingly, our findings reveal some remarkable results. Exploiting reinforcement learning-based adaptive networks improves cooperation when juxtaposed with existing PDGs performed on homogeneous networks. At the same time, the network's topology evolves from homogeneous to heterogeneous states. This change occurs as players gain experience from past games and become more astute in deciding whether to join PDGs with their current neighbors or disconnect from the least profitable neighbors. Instead, they seek out more favorable environments by establishing connections with second-order neighbors with higher rewards. By calculating the degree distribution and modularity of the adaptive network in a steady state, we confirm that the adaptive network follows a power law and has a clear community structure, indicating that the adaptive network is similar to networks in the real world. Our study reports a new phenomenon in evolutionary game theory on networks. It proposes a new perspective to generate scale-free networks, which is generating scale-free networks by the evolution of homogeneous networks rather than typical ways of network growth and preferential connection. Our results provide new aspects to understanding the network structure, the emergence of cooperation, and the behavior of actors in nature and society.

Replicator-mutator dynamics with evolutionary public goods game-environmental feedbacks.

Feedback loops between strategies and the environment are commonly observed in socio-ecological, evolution-ecological, and psychology-economic systems. However, the impact of mutations in these feedback processes is often overlooked. This study proposes a novel model that integrates the public goods game with environmental feedback, considering the presence of mutations. In our model, the enhancement factor of the public goods game combines positive and negative incentives from the environment. By employing replicator-mutator (RM) equations, we provide an objective understanding of the system's evolutionary state, focusing on identifying conditions that foster cooperation and prevent the tragedy of the commons. Specifically, mutations play a crucial role in the RM dynamics, leading to the emergence of an oscillatory tragedy of the commons. By verifying the Hopf bifurcation condition, we establish the existence of a stable limit cycle, providing valuable insights into sustained oscillation strategies. Moreover, the feedback mechanism inherent in the public goods game model offers a fresh perspective on effectively addressing the classic dilemma of the tragedy of the commons.

Reinforcement learning relieves the vaccination dilemma.

The main goal of this paper is to study how a decision-making rule for vaccination can affect epidemic spreading by exploiting the Bush-Mosteller (BM) model, one of the methodologies in reinforcement learning in artificial intelligence (AI), which can realize the systematic process of learning in humans, on complex networks. We consider the BM model with two stages-vaccination and epidemiological processes-and address two independent rules about fixed loss consideration and average payoff of neighbors to update agent's vaccination behavior for various stimuli, such as loss of payoffs and environments during the vaccination process. Higher sensitivity not only favors higher vaccination coverage rates but also delays the transition point in relative vaccination costs when transitioning from full vaccination (inoculation level 1) to incomplete vaccination (inoculation level less than 1). Extensive numerical simulations demonstrate that the vaccination dilemma can be overcome to some extent, and the distribution of the intended vaccination probabilities in both independent rules is either normal or skewed when different parameters are considered. Since AI is contributing to many fields, we expect that our BM-empowered learning can ultimately resolve the vaccination dilemma.

Enhancing coexistence of mobile species in the cyclic competition system by wildlife refuge.

We investigate evolving dynamics of cyclically competing species on spatially extended systems with considering a specific region, which is called the "wildlife refuge," one of the institutional ways to preserve species biodiversity. Through Monte-Carlo simulations, we found that the refuge can play not groundbreaking but an important role in species survival. Species coexistence is maintained at a moderate mobility regime, which traditionally leads to the collapse of coexistence, and eventually, the extinction is postponed depending on the competition rate rather than the portion of the refuge. Incorporating the extinction probability and Fourier transform supported our results in both stochastic and analogous ways. Our findings may provide valuable evidence to assist fields of ecological/biological sciences in understanding the presence and construction of refuges for wildlife with associated effects on species biodiversity.

Effects of species vigilance on coexistence in evolutionary dynamics of spatial rock-paper-scissors game.

Recognizing surrounding situations, such as enemy attacks, which can be realized by predator-prey relationships, is one of the common behaviors of the population in ecosystems. In this paper, we explore the relationship between such species' behavior and biodiversity in the spatial rock-paper-scissors game by employing the ecological concept "vigilance." In order to describe the vigilance process, we adopt a multiplex structure where two distinct layers describe virtual and physical interactions. By investigating the process of evolution in species, we also found that species with different vigilance go together. In addition, by utilizing the dynamic time warping method, we found that species with the same vigilance have consistent behavior, but species with different vigilance have diverse behavior. Our findings may lead to broader interpretations of mechanisms promoting biodiversity via vigilance in species ecosystems.

Effect of vaccine efficacy on disease transmission with age-structured.

Recent outbreaks of novel infectious diseases (e.g., COVID-19, H2N3) have highlighted the threat of pathogen transmission, and vaccination offers a necessary tool to relieve illness. However, vaccine efficacy is one of the barriers to eradicating the epidemic. Intuitively, vaccine efficacy is closely related to age structures, and the distribution of vaccine efficacy usually obeys a Gaussian distribution, such as with H3N2 and influenza A and B. Based on this fact, in this paper, we study the effect of vaccine efficacy on disease spread by considering different age structures and extending the traditional susceptible-infected-recovery/vaccinator(SIR/V) model with two stages to three stages, which includes the decision-making stage, epidemic stage, and birth-death stage. Extensive numerical simulations show that our model generates a higher vaccination level compared with the case of complete vaccine efficacy because the vaccinated individuals in our model can form small and numerous clusters slower than that of complete vaccine efficacy. In addition, priority vaccination for the elderly is conducive to halting the epidemic when facing population ageing. Our work is expected to provide valuable information for decision-making and the design of more effective disease control strategies.

MiR-5195-3p predicts clinical prognosis and represses colorectal cancer progression by targeting TLR4/MyD88 signaling.

BACKGROUND: Recent studies have highlighted the role of miR-5195-3p in suppressing cell growth in various cancers. However, the specific functional impact of miR-5195-3p in colorectal cancer (CRC) remain to be fully clarified. The importance of miR-5195-3p in CRC was evaluated, aiming to uncover its underlying molecular mechanism and identify it as a potential therapeutic target for CRC. RESULTS: Our research has shown that miR-5195-3p is markedly under-expressed in CRC tissues and cell cultures, with its reduced presence associated with a higher TNM stage, lymphatic invasion, and unfavorable survival outcome. Ectopic miR-5195-3p expression curtailed proliferation, migration, and invasion of SW1116 and HT29 cells. Additionally, we discovered that miR-5195-3p directly targets and negatively influences Toll-like receptor 4 (TLR4) in CRC cells. Moreover, an inverse relationship was noted between miR-5195-3p and TLR4 expression in CRC tissue samples. Notably, restoring TLR4 expression counteracted miR-5195-3p's suppressive impact on cell growth, motility, invasiveness, epithelial-mesenchymal transition (EMT), and the TLR4/MyD88 signaling pathway in SW1116 and HT29 cells. CONCLUSIONS: MiR-5195-3p suppresses the CRC cellular functions through the downregulation of TLR4/MyD88 signaling, indicating that targeting miR-5195-3p might offer a viable therapeutic strategy for CRC.

Understanding the role of neutral species by means of high-order interaction in the rock-paper-scissors dynamics.

The existence of neutral species carries profound ecological implications that warrant further investigation. In this paper, we study the impact of neutral species on biodiversity in a spatial tritrophic system of cyclic competition, in which the neutral species are identified as the fourth species that may affect the competition process of the other three species under the rock-paper-scissors (RPS) rule. Extensive simulations showed that neutral species can promote coexistence in a high mobility regime within the system. When coexistence occurs, we found that the state can be maintained by two mechanisms: Species can either (i) adhere to traditional RPS rule or (ii) form patches to resist invasion. Our findings might aid in understanding the impact of neutral species on biodiversity in ecosystems.

Assessing the medical resources in COVID-19 based on evolutionary game.

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (ß < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (ß > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality.

The effect of territorial awareness in a three-species cyclic predator-prey model.

Recognizing territories is essential to decide behavior of population either human or animals, and interaction between groups or individuals according to the territorial awareness is universal. Understanding various mechanisms which affect on such species behaviors can be possible by evolutionary games, and in particular, the rock-paper-scissors (RPS) game has been played a key role as a paradigmatic model to explore biodiversity from microbiota to societies. Among paramount mechanisms in systems of RPS, the role of intraspecific interaction has been recently noted in terms of promoting biodiversity. Since intraspecific interaction is defined by an invasive reaction between individuals in the same group, the interaction may be also sensitive to the territorial awareness. To explore how territorial awareness-based intraspecific interaction can affect species biodiversity, we endow species with the mechanism in the classic RPS game. By means of the Monte-Carlo method, we find the phenomenon that the presence of species' territorial awareness has an impact on intraspecific interaction which ultimately affects species biodiversity. At the same time, we also find that territorial awareness can play a significant role to the average waiting time for extinction which is numerically elucidated by exploiting the quantity: interface width statistic. Unlike prior research that concentrated solely on the relationship between interaction frequency and species diversity, our results shed lights on the important role of territorial awareness in models of RPS, and they reveal fascinating evolutionary outcomes in structured populations that are a unique consequence of such awareness behavior.

A three-arm, multicenter, open-label randomized controlled trial of hydroxychloroquine and low-dose prednisone to treat recurrent pregnancy loss in women with undifferentiated connective tissue diseases: protocol for the Immunosuppressant regimens for LIving FEtuses (ILIFE) trial.

BACKGROUND: Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressants to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD. METHODS: The Immunosuppressant for Living Fetuses (ILIFE) Trial is a three-arm, multicenter, open-label randomized controlled trial with the primary objective of comparing hydroxychloroquine combined with low-dose prednisone and anticoagulation with anticoagulation alone in treating UCTD women with recurrent spontaneous abortion. The third arm of using hydroxychloroquine combined with anticoagulant for secondary comparison. A total of 426 eligible patients will be randomly assigned to each of the three arms with a 1:1:1 allocation ratio. The primary outcome is the rate of live births. Secondary outcomes include adverse pregnancy outcomes and progression of UCTD. DISCUSSION: This is the first multi-center, open-label, randomized controlled trial which evaluates the efficacy of immunosuppressant regimens on pregnancy outcomes and UCTD progression. It will provide evidence on whether the immunosuppressant ameliorates the pregnancy prognosis in UCTD patients with RSA and the progression into defined connective tissue disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03671174 . Registered on 14 September 2018.

Melatonin prevents endothelial dysfunction in SLE by activating the nuclear receptor retinoic acid-related orphan receptor-α.

Atherosclerotic cardiovascular disease confers significant morbidity and mortality in patients with systemic lupus erythematosus (SLE). A substantial proportion of patients with SLE display accelerated endothelial dysfunction, which precedes cardiovascular disease. Melatonin and its nuclear receptor retinoid-related orphan receptor alpha (RORα) have been reported to have some protective effects on the development of atherosclerosis. However, the function of melatonin in SLE-induced endothelial dysfunction and the role that RORα plays are still unknown. In this study, we found that RORα protein expression was decreased in aortas of lupus-prone mice and in human umbilical vein endothelial cells (HUVECs) cultured with medium containing sera of patients with SLE. Melatonin-treated HUVECs showed a decrease of pro-inflammatory mRNAs [interleukin-1beta (IL-1ß), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α)] under the stimulation of SLE medium. Melatonin increased nitric oxide and antioxidant mRNAs (SOD1, GPX1, and CAT) and downregulated reactive oxygen species (ROS) level in HUVECs, which may subsequently delay endothelial senescence and promote HUVEC proliferation and repair after injury. Melatonin inhibited SLE medium-induced RAW264.7 macrophage migration. HUVECs pretreated with melatonin expressed less adhesion-related proteins (ICAM-1 and VCAM-1); as a result, these cells adhered to fewer peripheral blood monocytes. In addition, we also showed that the protective effects of melatonin on endothelial cells were largely diminished when RORα was knockdown in HUVECs. In conclusion, by targeting the nuclear receptor RORα, melatonin preserves normal functions of endothelium in SLE by its anti-inflammatory, antioxidant, and anti-senescence effects. RORα may have the potential to become a prophylactic or therapeutic target in preventing endothelial dysfunction and atherosclerotic cardiovascular disease in patients with SLE.