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Pancreatic ductal adenocarcinoma (PDAC) is highly lethal and resistant to conventional therapies, including chemo‐, radio‐, and immunotherapy. In this study, it is first determined that a combination of dihydroartemisinin (DHA) and RSL‐3 (a glutathione peroxidase 4 (GPX4) inhibitor) markedly induced ferroptosis of PDAC tumor cells. A mechanistic study revealed that DHA can react with iron ions to generate carbon radicals and deplete intracellular glutathione, thereby cumulatively triggering the lipid peroxidation of tumor cells with RSL‐3‐mediated GPX4 inhibition. A DHA‐conjugated amphiphilic copolymer is subsequently synthesized, and intracellular acidity and oxidation dual‐responsive DHA nanoparticles are further engineered for the tumor‐specific co‐delivery of DHA and RSL‐3. The resultant nanoparticles (PDBA@RSL‐3) efficiently induce ferroptosis of tumor cells in the Panc02 tumor‐bearing immune‐deficient mouse model, and elicit T‐cell‐based antitumor immunity in the immune‐competent mouse model. The combination of PDBA@RSL‐3 nanoparticles and programmed death ligand 1 blockade therapy efficiently inhibits PDAC tumor growth in the immune‐competent mouse models. This study may provide novel insights for treatment of PDAC with ferroptosis‐based immunotherapy. [ABSTRACT FROM AUTHOR]

Adolescence is a high‐risk age for exposure to violent media (EVM) and bullying. Some previous theories and empirical studies have highlighted a moderated mediating model that normative beliefs about aggression (NBA) as a mediator and self‐control (SC) as a moderator for the link between EVM and aggressive behaviors (including bullying behaviors). However, most previous studies analyzed traditional bullying (TB) and cyberbullying (CB) separately, which is not conducive to finding the differences between the two bullying behaviors. Therefore, this study aims to compare the differences between risk prediction models of TB and CB among adolescents. A total of 777 Chinese adolescent students (336 girls; Mage = 13.57 ± 0.98) completed questionnaires including EVM, NBA, TB, CB, and SC. The results showed that: (1) EVM was positively related to adolescent TB/CB; (2) NBA mediated the above relations; and (3) SC buffers the direct effect of EVM on TB and the effect of NBA on TB. However, SC buffers the effect of NBA on adolescent CB but not buffers the direct effect of EVM on CB. This study highlights the necessity of distinguishing offline and online situations in aggressive behavior research. We suggested "online disinhibit hypothesis" would be adopted to explain why protector factors (e.g., SC) do not buffer the link between aggression‐related risk factors (e.g., EVM) and online aggression (e.g., CB). [ABSTRACT FROM AUTHOR]

As a classic NP‐hard problem in machine learning and computational geometry, the k‐means problem aims to partition the given points into k sets to minimize the within‐cluster sum of squares. The k‐means problem with penalties (k‐MPWP), as a generalizing problem of the k‐means problem, allows a point that can be either clustered or penalized with some positive cost. In this paper, we mainly apply the parallel seeding algorithm to the k‐MPWP, and show sufficient analysis to bound the expected solution quality in the case where both the number of iterations and the number of points sampled in each iteration can be given arbitrarily. The approximate guarantee can be obtained as O(f(M)lnk), where f(M) is a polynomial function involving the maximal ratio M between the penalties. On one hand, this result can be viewed as a further improvement on the parallel algorithm for k‐MPWP given by Li et al., where the number of iterations depends on other factors. On the other hand, our result also generalizes the one solving the k‐means problem presented by Bachem et al., because k‐MPWP is a variant of the k‐means problem. Moreover, we present a numerical experiment to show the effectiveness of the parallel algorithm for k‐means with penalties. [ABSTRACT FROM AUTHOR]

Background: Immune dysfunction in Alzheimer's disease (AD) was previously thought to be limited to the central nervous system, but recent studies suggest that the peripheral immune system also plays a key role. This study compared and analyzed the changes in peripheral immune cells in patients with AD and mild cognitive impairment (MCI) and their correlation with cognition, and combined 18F‐FDG PET and 18F‐AV45 PET to investigate the role of peripheral immune cells in AD pathology and the possibility as biomarkers for early clinical diagnosis and disease assessment. Methods: The 146 participants included 70 AD patients, 26 MCI patients, and 50 controls. 34 AD patients tested with 18F‐AV45 (18F ‐Florbetapir) positron emission tomography (PET). 23 were Aβ‐positive (A+), and 11 were Aβ‐negative (A‐). All participants had a peripheral immune cell, cognitive evaluation, and detailed nervous system examination. Results: (1) Significant differences in peripheral immune cells in AD compared with MCI and CG; (2) There was no significant correlation between NEU%, NLR, LY, and LY% and cognitive scale scores for patients in the AD and A+ groups, while there was a significant correlation with cognitive scale scores in the MCI and A‐ groups; and (3) Peripheral immune cells NEU%, NLR, LY, and LY% in A+ patients were correlated with FDG metabolism in several functional brain areas and Aβ load in some brain areas, but not with Aβ load in all functional brain areas in A‐ patients. Conclusion: Differences in peripheral immune cells help to distinguish AD from MCI, with NLR having better diagnostic efficacy. peripheral immune cells may have a greater impact on early cognitive dysfunction; NEU%, NLR, LY, and LY% may be associated with Aβ deposition and could serve as potential biomarkers for early clinical diagnosis and disease assessment in AD. [ABSTRACT FROM AUTHOR]