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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]

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]

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]

This study investigated attentional capture by individuals with cognitive vulnerability to depression (CVD), by using irrelevant emotional distractor faces. The hypothesis was that, during face-orientation decision tasks, both happy and sad task-irrelevant emotional faces are more attractive to individuals with CVD than to controls. To test this, both a group of subjects with CVD (n = 45) and a control group without such vulnerability (n = 51) were asked to search for a male face among two presented female faces based on the Chinese affective picture system. Although the attentional processing of emotionally facial expressions had a slower reaction time (RT) than that of neutral facial expressions, the presence of faces that express happiness did not trigger significantly different RTs between both groups. However, the presence of faces that express sadness resulted in longer RTs in individuals with CVD compared to controls. In summary, these results suggest that a focus on negative information and a difficulty to disengage from negative information may be characteristics of individuals with CVD. These characteristics could lead to a higher depression risk. The implications of these findings can be used for cognitive training of attentional bias with the aim to prevent the development of depression. [ABSTRACT FROM AUTHOR]

Background: Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition are prevalent malnutrition issues that disproportionately affect low-income countries and pose significant risks to the health and development of children and adolescents. This study offers a detailed examination of these deficiencies' prevalence trends and gender and regional variations using Global Burden of Disease Study data from 1990 to 2019. It also assesses the specific impact on various age groups, providing essential insights for targeted health interventions and policy-making., Methods: Data spanning from 1990 to 2019 on Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition were extracted from the 2019 Global Burden of Disease Study. Age-Standardized Incidence Rates (ASR) were computed by gender, region, and etiology, utilizing the estimated annual percentage change (EAPC) to assess temporal trends., Results: In 2019, Central Sub-Saharan Africa had the highest prevalence of Vitamin A deficiency, particularly among males, and iodine deficiency peaked in the same region for both genders. South Asia had the highest incidence of protein-energy malnutrition for both genders. Regions with a low Socio-Demographic Index (SDI) showed lower ASR for these deficiencies. Notably, Cameroon, Equatorial Guinea, and Maldives recorded the highest ASR for vitamin A deficiency, iodine deficiency, and protein-energy malnutrition, respectively. The declining ASR trend for vitamin A deficiency, especially among males, suggests effective interventions. East Asia saw a significant increase in iodine deficiency ASR from 1990 to 2019, particularly among women, requiring targeted interventions. The rising ASR of protein-energy malnutrition in several regions, especially among men, raises concerns. Vitamin A deficiency primarily affected children and adolescents, iodine deficiency predominantly impacted adolescents and young adults, and protein-energy malnutrition was chiefly observed among children under 5 years old. These findings underscore the necessity for tailored interventions considering age-specific nutritional needs and challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ji, Zhou, Zhao, Chen and Su.)

Introduction: Periodontal disease (PD) presents a substantial global health challenge, encompassing conditions from reversible gingivitis to irreversible periodontitis, often culminating in tooth loss. The gut-oral axis has recently emerged as a focal point, with potential gut microbiota dysbiosis exacerbating PD., Methods: In this study, we employed a double-sample bidirectional Mendelian randomized (MR) approach to investigate the causal relationship between specific gut microbiota and periodontal disease (PD) and bleeding gum (BG) development, while exploring the interplay between periodontal health and the gut microenvironment. We performed genome-wide association studies (GWAS) with two cohorts, totalling 346,731 (PD and control) and 461,113 (BG and control) participants, along with data from 14,306 participants' intestinal flora GWAS, encompassing 148 traits (31 families and 117 genera). Three MR methods were used to assess causality, with the in-verse-variance-weighted (IVW) measure as the primary outcome. Cochrane's Q test, MR-Egger, and MR-PRESSO global tests were used to detect heterogeneity and pleiotropy. The leave-one-out method was used to test the stability of the MR results. An F-statistic greater than 10 was accepted for instrument exposure association., Results and Conclusion: Specifically, Eubacterium xylanophilum and Lachnoclostridium were associated with reduced gum bleeding risk, whereas Anaerotruncus , Eisenbergiella , and Phascolarctobacterium were linked to reduced PD risk. Conversely, Fusicatenibacter was associated with an elevated risk of PD. No significant heterogeneity or pleiotropy was detected. In conclusion, our MR analysis pinpointed specific gut flora with causal connections to PD, offering potential avenues for oral health interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Shao, Zhou, Yu, Wang, Wang and Cai.)

Prostate cancer has a heterogeneous prognosis. Most previous studies have focused on the identification of prognostic biomarkers in the prostate cancer tumor. However, it is increasingly recognized that the tumor microenvironment contributes to prostate cancer aggressiveness and progression. We therefore examined whole transcriptome expression of the prostate stroma and associations with aggressive and lethal prostate cancer. We performed RNA sequencing (Illumina TruSeq Exome Capture) of 272 tumor-adjacent and 120 benign-adjacent macrodissected prostate stromal samples from 293 men with prostate cancer from the Health Professionals Follow-up Study and Physicians' Health Study. We performed differential expression analysis comparing gene expression and pathways by Gleason score and lethal outcome. We also tested a previously developed stromal gene signature of Gleason score in these datasets. Comparing high- with low-Gleason score cancers, 26 genes (P < 0.001) and 12 pathways (FDR < 0.20) were significantly differentially expressed in tumor-adjacent stroma, including pathways related to stroma composition remodeling and DNA repair, with 73 genes and 65 pathways significant in benign-adjacent stroma. Comparing lethal with nonlethal prostate cancer, 11 genes were differentially expressed in tumor-adjacent and 15 genes in benign-adjacent stroma, and pathways involved in inflammatory response were differentially enriched in both tumor and benign-adjacent stroma. In addition, our previously identified Gleason stromal gene signature was validated to be associated with Gleason score in these data. Implications: Our study uncovers stroma-specific genes and pathways that are differentially enriched with high Gleason score and lethal prostate cancer, demonstrating that the molecular investigation of the tumor microenvironment can provide additional information about prostate cancer prognosis., (©2022 American Association for Cancer Research.)

Hormonal therapy targeting androgen receptor (AR) is initially effective to treat prostate cancer (PCa), but it eventually fails. It has been hypothesized that cellular heterogeneity of PCa, consisting of AR + luminal tumor cells and AR - neuroendocrine (NE) tumor cells, may contribute to therapy failure. Here, we describe the successful purification of NE cells from primary fresh human prostate adenocarcinoma based on the cell surface receptor C-X-C motif chemokine receptor 2 (CXCR2). Functional studies revealed CXCR2 to be a driver of the NE phenotype, including loss of AR expression, lineage plasticity, and resistance to hormonal therapy. CXCR2-driven NE cells were critical for the tumor microenvironment by providing a survival niche for the AR + luminal cells. We demonstrate that the combination of CXCR2 inhibition and AR targeting is an effective treatment strategy in mouse xenograft models. Such a strategy has the potential to overcome therapy resistance caused by tumor cell heterogeneity., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Baicalin, an active flavone isolated from Scutellaria baicalensis Georgi, has been demonstrated to induce various beneficial biochemical effects such as anti‑inflammatory, anti‑viral, and antitumor effects. However, the antitumor mechanism of baicalin is not well understood. In the present study, baicalin was demonstrated to inhibit the viability and migration of a widely used ovarian cancer cell line, A2780, in a dose‑dependent manner. MTT assays revealed that cell viability significantly decreased in ovarian cancer cells treated with baicalin compared with untreated cells, without effect on normal ovarian cells. Flow cytometric analysis indicated that baicalin suppressed cell proliferation by inducing apoptosis. The underlying mechanisms involved were indicated to be downregulation of the anti‑apoptotic protein B‑cell lymphoma 2 apoptosis regulator and activation of caspase‑3 and ‑9. In addition, wound healing and transwell assays revealed that cell migratory potential and expression of matrix metallopeptidase (MMP)‑2 and MMP‑9 were significantly inhibited when cells were exposed to baicalin, compared with untreated cells. The present study therefore suggested that baicalin has the potential to be used in novel anti‑cancer therapeutic formulations for treatment of ovarian cancer.

Familiar chunks can be processed highly efficiently, and this automatic process can prohibit the problem solver from developing novel and original ways to creatively solve difficult problems. For this reason, the role of the reverse process, chunk decomposition (CD), the process by which familiar patterns are broken down into their component elements in order to be regrouped in another meaningful manner, has been generally recognized as part of the creative process. However, previous studies on this issue have mainly focused on the decomposition process of CD (the D-process), while the reorganization process of CD has been greatly neglected or has not been distinctively identified in previous work. In this paper, we argue that the R-process could be equally as important as the D-process for CD. Even if a problem solver manages to decompose a familiar chunk into its elements, he or she still may not solve the problem if these elements are not successfully organized in a new and meaningful manner. To investigate whether the cognitive mechanism of the R-process is different from that of the D-process, we designed an experiment for detecting the effects of chunk tightness, which is regarded as the key factor in CD and which can be experimentally manipulated by the radical-level (loose) and stroke-level (tight) Chinese character CD tasks in the D-process, the R-process, and the more purified organization task (the O-process task) that does not involve the decomposition process. Our results showed that the stroke-level (tight) task was more difficult than the radical-level (loose) task for the D-process. However, for the R-process, the stroke- and radical-level tasks showed no differences in performance. Moreover, for the more purified reorganization task, the O-process task, the radical-level organization and reorganization could be even more difficult than the stroke-level organization and reorganization. This result demonstrated that the cognitive processes underlying chunk decomposition and reorganization are fundamentally different. Therefore, more general concepts such as chunk restructuring that could include both D- and R-processes might be more suitable in accounting for this type of creative insight.

Scutellaria altissima L. is a common traditional Chinese medicine used to treat inflammation in some countries. Scutellarin, an active major flavone glycoside isolated from the traditional Chinese medicine Scutellaria altissima L., has been shown to offer various beneficial biochemical effects on cerebrovascular diseases and inflammation. However, the antiproliferative effects of Scutellarin in prostate cancer and the underlying mechanism are not fully elucidated. In the present study, we aimed to ascertain whether Scutellarin inhibits cancer cell growth and to further explore the molecular mechanism. Scutellarin enhanced the sensitivity of prostate cancer cells to cisplatin. MTT assays revealed that cell viability was significantly decreased in the prostate cancer cells treated with Scutellarin. Flow cytometric analysis indicated that Scutellarin suppressed cell proliferation by promoting G2/M arrest and inducing apoptosis. We employed western blotting to delineate the underlying mechanisms involved in the G2/M arrest and apoptosis. Comet assay and γH2AX immunocytochemistry were used to detect levels of DNA damage in PC3 cells exposed to Scutellarin and/or cisplatin. Our data revealed that Scutellarin significantly induced prostate cancer cell apoptosis by activating the caspase cascade. An increase in the Bax/Bcl-2 ratio, depolarization of mitochondrial membrane potential and cell cycle arrest at G2/M phase were accompanied by the apoptosis induction. Additionally, Scutellarin altered the protein expression of cell cycle and apoptosis regulatory genes by downregulating Cdc2, cyclin B1 and Bcl-2 and upregulating caspase-3, caspase-9 and Bax in prostate cancer cells. Furthermore, Scutellarin sensitized PC3 cells to cisplastin treatment in a dose-dependent manner. Taken together, our data confirmed the cytotoxicity of Scutellarin against prostate cancer PC3 cells and provide new findings in regards to Scutellarin sensitizing prostate cancer cells to chemotherapy. Our findings suggest that Scutellarin has potential to be used as a novel antineoplastic therapeutic candidate for prostate cancer patients.