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This paper investigates a nonlinear multi-player non-zero-sum differential game with state constraints and input delay. To solve this problem, this paper constructs a neural network (NN) framework to approximate the solution of the Hamilton-Jacobi-Isaacs equation. The adaptive dynamic programming method is utilized where each player only needs one critic NN. To solve the issue of state saturation and input delay, this paper develops a novel state constraints mechanism for the differential game to make the states within the predetermined constraint set. Then, a future predictor is employed to compensate for the input delay. The condition that estimated states of agents having nonlinear dynamics with the predictor converge to the real state is derived. With these treatments, the system is more in line with real-world applications. Moreover, the stability of the system is also analyzed using the Lyapunov theorem. Simulation examples are given to validate the efficiency of the presented methods. [ABSTRACT FROM AUTHOR]

This paper investigates a nonlinear two‐player non‐zero‐sum differential game with state and input constraints. To solve this problem, this paper constructs a neural network (NN) framework to approximate the solution of the Hamilton‐Jacobi‐Isaacs (HJI) equation. The adaptive dynamic programming (ADP) method is utilized where each player only needs one critic NN. To solve the issue of state and input saturations, this paper develops a novel constrained system for the differential game, firstly to make the states within the predetermined constraint set. Then, the non‐quadratic expression is used to substitute the traditional quadratic expression for the two‐player non‐zero‐sum differential game, and both of the inputs of the two players are constrained. With these treatments, the control input and the system are more in line with real‐world applications. Moreover, the stability of the system is also analyzed using the Lyapunov theorem. Two numerical examples are presented to illustrate that the critic NN weights estimation errors and the system are uniformly ultimately bounded (UUB), and the state and input constraints can be achieved. [ABSTRACT FROM AUTHOR]

This article investigates a multiplayer nonzero‐sum differential game (MNDG) with switching topology and input delay. The Hamilton–Jacobi–Isaacs (HJI) equation is used to derive the optimal control strategies. To solve the issue of switching topology, the control strategies are decoupled with the communication topology. Then, the stability of the system can be achieved regardless of changes in communication topology with the designed control strategies. This does not require a restriction on the dwell time, making the system stability conditions more relaxed. The Lyapunov–Krasovskii functional (LKF) is constructed to prove the stability of the system in the presence of time‐varying input delay. To cope with the real‐world situation, the input delay is considered to be disturbed by a time‐varying perturbation in this article. With these treatments, the system is more in line with real‐world applications. Simulation examples are given to validate the efficiency of the presented methods. [ABSTRACT FROM AUTHOR]

This paper investigates a multi‐pursuer single‐evader nonzero‐sum differential game. Unlike traditional treatments, cooperative tracking is considered to design the optimal pursuit strategy by introducing a novel weighted topology and a scalar coupling gain. First, the distributed control strategy is designed based on the Hamilton–Jacobi–Isaacs (HJI) under the nonzero‐sum differential game. Then the modified LQR‐based cooperative tracking strategy is applied to achieve cooperativity among all the pursuers. The interception condition is also analyzed using a coupling gain based on the Laplacian matrix. Several illustrative examples under different scenarios are presented, and the results show that the pursuers with the proposed strategy can successfully intercept the evader. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) represents a significant global health challenge with high incidence and mortality rates. T cells and natural killer (NK) cells are pivotal in this context, yet HCC can evade immune surveillance. CD161 (KLRB1), a C-type lectin receptor, modulates immune responses and is expressed on NK cells and a subset of T cells. Its relevance in HCC remains poorly understood, with conflicting findings regarding its impact on patient prognosis. Methods: Utilizing TCGA data and single-cell analysis, we investigated the biological functions of KLRB1 in HCC. Peripheral blood samples from 126 HCC patients were collected to assess KLRB1 expression on NK and T cells. The diagnostic performance of KLRB1 on NK and CD8 + T cells was evaluated using receiver operating characteristic curve (ROC) analysis, while its prognostic significance was assessed using Kaplan-Meier analysis and COX regression models. Results: Analysis of TCGA data revealed a significant correlation between KLRB1 expression and immune activation, particularly T cell activation. Single-cell data further demonstrated elevated KLRB1 expression in tissue-resident NK and T cells within HCC, which co-expressed markers of immune activation. Clinical data showed downregulated KLRB1 expression on NK and T cells in HCC patients compared to health individuals, with lower expression levels correlating with poorer prognosis. Conclusion: KLRB1 emerges as a promising biomarker in HCC, with its downregulation on peripheral blood NK and T cells suggesting potential prognostic value. Further elucidation of KLRB1's role in HCC may pave the way for the development of targeted immunotherapies and the improvement of patient outcomes. [ABSTRACT FROM AUTHOR]

Neuroendocrine (NE) cells comprise ~1% of epithelial cells in benign prostate and prostatic adenocarcinoma (PCa). However, they become enriched in hormonally treated and castration‐resistant PCa (CRPC). In addition, close to 20% of hormonally treated tumors recur as small cell NE carcinoma (SCNC), composed entirely of NE cells, which may be the result of clonal expansion or lineage plasticity. Since NE cells do not express androgen receptors (ARs), they are resistant to hormonal therapy and contribute to therapy failure. Here, we describe the identification of glypican‐3 (GPC3) as an oncofetal cell surface protein specific to NE cells in prostate cancer. Functional studies revealed that GPC3 is critical to the viability of NE tumor cells and tumors displaying NE differentiation and that it regulates calcium homeostasis and signaling. Since our results demonstrate that GPC3 is specifically expressed by NE cells, patients with confirmed SCNC may qualify for GPC3‐targeted therapy which has been developed in the context of liver cancer and displays minimal toxicity due to its tumor‐specific expression. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

An understanding of the molecular features associated with prostate cancer progression (PCa) and resistance to hormonal therapy is crucial for the identification of new targets that can be utilized to treat advanced disease and prolong patient survival. The glycome, which encompasses all sugar polymers (glycans) synthesized by cells, has remained relatively unexplored in the context of advanced PCa despite the fact that glycans have great potential value as biomarkers and therapeutic targets due to their high density on the cell surface. Using imaging mass spectrometry (IMS), we profiled the N-linked glycans in tumor tissue derived from 131 patients representing the major disease states of PCa to identify glycosylation changes associated with loss of tumor cell differentiation, disease remission, therapy resistance and disease recurrence, as well as neuroendocrine (NE) differentiation which is a major mechanism for therapy failure. Our results indicate significant changes to the glycosylation patterns in various stages of PCa, notably a decrease in tri- and tetraantennary glycans correlating with disease remission, a subsequent increase in these structures with the transition to therapy-resistant PCa, and downregulation of complex N-glycans correlating with NE differentiation. Furthermore, both nonglucosylated and monoglucosylated mannose 9 demonstrate aberrant upregulation in therapy-resistant PCa which may be useful therapeutic targets as these structures are not normally presented in healthy tissue. Our findings characterize changes to the tumor glycome that occur with hormonal therapy and the development of castration-resistant PCa (CRPC), identifying several glycan markers and signatures which may be useful for diagnostic or therapeutic purposes. [ABSTRACT FROM AUTHOR]

This multi-wave longitudinal study examined the role of depressive symptoms and the weakest link approach as an indicator of cognitive vulnerability to predict stress generation. The weakest link approach posits that an individual is as cognitively vulnerable as his or her strongest attributional style. Data of 521 Chinese adolescents were investigated in this study. During an initial assessment, participants completed a demographic survey that assessed depressive symptoms, weakest links, and stress. Over the subsequent 6 months, participants completed monthly assessments of depressive symptoms and stress. The results indicated that both depressive symptoms and weakest link approach predict the generation of stress. High scores of depressive symptoms were associated with high levels of both independent stress and dependent stress. High weakest link scores predicted an increase of dependent stress. For the follow-up interval, the interaction of weakest link × depressive symptoms was a significant predictor for dependent stress but not for independent stress. In addition, gender difference was identified as a predictor of the stress generation effect. Compared with adolescent boys, adolescent girls tended to experience higher levels of dependent stress. These results suggest that depressive symptoms and cognitive vulnerability are important for the prediction of stress generation in Chinese adolescents. [ABSTRACT FROM AUTHOR]

The current study examined the potential moderating effects of negative cognitive styles on the relationship between daily hassles and depressive symptoms among COVID-19 home quarantined university students. A total of 686 university students ranging in age from 16 to 23 years old (M = 19.04 years, SD = 1.06 years) participated in the study. At the time of the study, they had six months' experience of COVID-19. The participants completed measures assessing daily hassles, cognitive styles, and depressive symptoms. Moderation analysis showed high levels of negative cognitive styles coping with daily hassles following the COVID-19 outbreak were associated with greater increases in depressed affect and anhedonia symptoms, but not somatic symptoms and interpersonal concerns. We conclude that negative cognitive styles influence vulnerability to depressive symptoms from daily hassles with home quarantine during the COVID-19 outbreak. [ABSTRACT FROM AUTHOR]