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Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders., Competing Interests: Declarations. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

The magnetospheric cusp connects the planetary magnetic field to interplanetary space, offering opportunities for charged particles to precipitate to or escape from the planet. Terrestrial cusps are typically found near noon local time, but the characteristics of the Jovian cusp are unknown. Here we show direct evidence of Jovian cusps using datasets from multiple instruments onboard Juno spacecraft. We find that the cusps of Jupiter are in the dusk sector, which is contradicting Earth-based predictions of a near-noon location. Nevertheless, the characteristics of charged particles in the Jovian cusps resemble terrestrial and Saturnian cusps, implying similar cusp microphysics exist across different planets. These results demonstrate that while the basic physical processes may operate similarly to those at Earth, Jupiter's rapid rotation and its location in the heliosphere can dramatically change the configuration of the cusp. This work provides useful insights into the fundamental consequences of star-planet interactions, highlighting how planetary environments and rotational dynamics influence magnetospheric structures., (© 2024. The Author(s).)

Background: Conventionally, the judgment of whether small pulmonary nodules are invasive is mainly made by thoracic surgeons according to the chest computed tomography (CT) features of patients. However, there are limits to how much useful information can be obtained from this approach. A large number of feature information was extracted from CT images by CT radiomics. The machine learning algorithm was used to construct models based on radiomic characteristics to predict the invasiveness of lung adenocarcinoma (LUAD) with a good prediction accuracy., Methods: A total of 416 patients with pathologically confirmed preinvasive lesions and LUAD after video-assisted thoracoscopic surgery (VATS) in the Department of Thoracic Surgery of the First People's Hospital of Yunnan Province from February 2020 to February 2022 were retrospectively analyzed. According to random classification, patients were divided into 2 groups. The RadCloud platform was used to extract radiomics features, and the most relevant radiomics features were selected by continuous dimension reduction method. Then, 6 machine learning algorithms were used to establish and verify the prediction model of small lung nodular adenocarcinoma invasiveness. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to evaluate the predictive performance., Results: There were 78 cases of pre-invasive lesions and 226 cases of invasive lesions in the training group, and 34 cases of pre-invasive lesions and 78 cases of invasive lesions in the validation group. In the training group, the AUC values of the 6 models were all more than 0.914, the 95% confidence interval (CI) was 0.857-1.00, the sensitivity was equal or more than 0.87, and the specificity was equal or more than 0.85. In the validation group, the AUC values of the 6 models were all equal or more than 0.732, the 95% CI was 0.651-1.00, the sensitivity was equal or more than 0.7, and the specificity was more than 0.77., Conclusions: Machine learning algorithms were used to construct models to predict the invasiveness of small nodular LUAD based on radiomics features, which it could provide more evidence for doctors to make diagnoses and more personalized treatment plans for patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-82/coif). The authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Based on the structural modification of regorafenib, 28 pyrazinyl-aryl urea derivatives were synthesized and their in vitro antiproliferative activities were evaluated. Six compounds (5-16, 5-17, 5-18, 5-19, 5-22, and 5-23) exhibited favorable inhibitory activity against the human bladder cancer T24 cell line, and 5-23 demonstrated the strongest inhibitory activity (IC 50 = 4.58 ± 0.24 μM) with high selectivity. Compound 5-23 induced apoptosis in the low concentration range (≤7.5 μM) combined with shorter incubation time (≤10 h) via the activation of caspases, while high concentrations and prolonged incubation times led to necroptotic cell death by activating the RIPK1/RIPK3/MLKL signaling pathway. Induced apoptosis and necroptosis were closely associated with intracellular reactive oxygen species generation and decreased mitochondrial membrane potential. Compared with regorafenib, 5-23 displayed improved pharmacokinetic profiles in an in vivo rat model. Molecular docking and structure-activity relationship analyses were in agreement with the biological data. Compound 5-23 may be a potent anti-bladder cancer agent and this small molecule can be considered as a promising structure for further optimization., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC 50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc - /GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents' discovery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)